Category Archives: Cell Medicine

Global Immune Repertoire Sequencing Market: Introduction

Immune repertoire is the sum of T cell receptors and B cell receptors that make an organism's adaptive immune system.It is extensively used in biomarker discovery to improve the success rate and cost-effectiveness of rational drug development. Advancements in next generation sequencing (NGS) have facilitated the development of a prevailing new technology known as immune repertoire sequencing for probing the complimentary determining region of these receptors. Immune repertoire sequencing targets T and B-lymphocytes and utilizes the 5 Rapid Amplification of cDNA Ends (RACE) Technology.

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Global Immune Repertoire Sequencing Market: Trends, Drivers, Restraints

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Immune Repertoire Sequencing Market: Increase in government support for pharmacogenomics-based drug recovery is the major driver of the market -...

Researchers at Yale and the Weizmann Institute of Science have found the first evidence that the human fetus can spontaneously produce insulin outside the pancreas in the small intestine, specifically a startling discovery that stands in contrast to the longheld belief that insulin production is unique to the pancreas.

While other researchers had previously been able to manipulate the proteins that regulate insulin secretion thereby getting other cells to produce insulin there have been no previous reports of other cells (outside of the pancreas) making insulin on their own.

Insulin is known to be produced by pancreatic cells to regulate glucose levels in the blood. It is also a growth factor. Destruction of insulin-producing cells in the pancreas causes Type 1 diabetes, while Type 2 is triggered by insulin resistance. The possibility that other cells are able to produce insulin can open up new avenues for diabetes treatment, researchers say. It also suggests that insulin might be involved in intestinal growth in the fetus.

The findings are published in the December issue of Nature Medicine.

For the study, researchers analyzed single cell data on both fetal tissue and neonatal tissue. When they first noted insulin-producing cells in the gut, they were surprised.

It was completely serendipitous, said Dr. Liza Konnikova, an assistant professor in pediatrics and obstetrics, gynecology and reproductive sciences at Yale School of Medicine, a member of the Human and Translational Immunology Program, and co-senior author of the study. The more we looked into it, we realized that insulin was originating from within the small intenstine. We were able to show that both the RNA and the protein are made in the small intestinal cells. Moreover, signaling for insulin production is also intact in these cells.

For the study, the researchers wanted to see what the transcriptional or RNA differences were between the fetus, which is not exposed to an abundant microbiome and is continuously developing, and newborns, who are exposed to an abundant microbiome. Looking at how immune and epithelial development are different between the fetuses and newborns highlighted not only the existence of intestinal insulin-producing cells, but also their complete expression signature. This could provide avenues through which this dormant ability might be awakened in adults.

Cells in the intestinal tract are a wonderful potential source of insulin because they are continuously renewed from intestinal stem cells, said co-lead author Shalev Itzkovitz, associate professor at the Weizmann Institute of Science, a research institution based in Israel. This could be an advantage in Type 1 diabetes, where insulin-producing cells are under attack from our immune system.

Other authors on the study included Dhana Llivichuzhca-Loja and Blake McCourt from the Yale School of Medicine.

Excerpt from:
Cell types outside the pancreas make insulin, too, study shows - Yale News

BIRMINGHAM, Ala. A clinical-stage biopharmaceutical company developing intellectual property licensed from the University of Alabama at Birmingham and two other institutions is testing its technology to treat glioblastoma multiforme, the most aggressive type of cancer that originates in the brain.

In a preclinical study published in the Nature portfolio journal Scientific Reports, researchers led by Larry Lamb, Ph.D., former associate professor of medicine at UAB, scientific co-founder and current chief scientific officer at IN8bio Inc., report that IN8bios proprietary Drug Resistant Immunotherapy (DRI) technology resulted in significant improvement of survival outcomes in a mouse model of human primary high-grade gliomas. A Phase I interventional clinical trial is being conducted at UAB of IN8bios INB-200, the DRI technology, in adults with newly diagnosed glioblastoma multiforme who are also receiving temozolomide (TMZ) chemotherapy. The clinical trial is led by Burt Nabors, M.D., professor in theUAB Department of Neurology.

DRI was developed based on two observations. First, when tumors are damaged by TMZ treatment, they develop stress-induced ligands on the cell surface. Normally, these signals would incite the immune watchdog gamma-delta T cells to recognize and kill the damaged tumor cells, through their ability to differentiate between healthy and diseased tissue. However, the second observation reveals a problem TMZ therapy kills lymphatic immune cells, including the gamma-delta T cells. This hinders the immune systems ability to leverage the TMZ-induced state of increased tumor vulnerability.

In DRI, peripheral blood mononuclear cells are collected from the mouse or patient. The gamma-delta T cells in that collection are purified, and then they are given a gene that makes them resistant to TMZ. Next, the drug-resistant gamma-delta T cells are expanded and reintroduced into the mouse or patient, concomitantly with TMZ chemotherapy. The resistant gamma-delta T cells should then be able to recognize the stress-induced ligands on the surface of TMZ-treated tumor cells and start to eliminate them.

In the Scientific Reports study, intracranial tumors were established in the mice using classical or mesenchymal patient-derived xenolines of glioblastoma.

In the UAB clinical trial, IN8bio earlier this year successfully completed treatment of the first cohort of three newly diagnosed glioblastoma patients, using its genetically modified gamma-delta T cell candidate for treating the solid tumors, says William Ho, CEO and co-founder of IN8bio. The gamma-delta T cell treatment, called INB-200, was generally well tolerated by the three patients, with no observed infusion reactions, cytokine release syndrome, neurotoxicity or dose limiting toxicities, the company reported at the 2021 American Society of Clinical Oncology Annual Meeting. All three patients exceeded their expected median progression-free survival based on their respective age and O-6-methylguanine-DNA methyltransferase status. Additional data from this Phase I trial is expected later this year. The second cohort of patients will receive multiple repeat doses of the DRI gamma-delta T cells.

IN8bio is the first company to advance genetically modified gamma-delta T cells into the clinic. The company is located in New York City, while its primary scientific operations remain in Birmingham, Alabama.

This summer, IN8bio completed an initial public offering of 4 million shares of common stock at an offering price of $10 per share. Net proceeds for IN8bio after expenses were $32.6 million.

This coming year, the IN8bio research lab expects to graduate from Birminghams Innovation Depot a business incubator into a new, 10,440-square-foot IN8bio lab and office space in the Martin Biscuit building at Birminghams Pepper Place, Second Avenue South and 29th Street, which is currently under development.

Ho says the IN8bio DRI approach targets an evolutionarily conserved pathway, the DNA Damage Response, that has potential applicability across a broad range of solid and liquid tumors for which chemotherapy remains the mainstay of treatment.

This includes potentially combining INB-200 with other approaches such as checkpoint inhibitors and other targeted therapies in orthogonal combinations to maximize the tumor impact, Ho said. Combined with our expertise in genetically engineering these cells ex-vivo, we look forward to continuing to develop our deep pipeline of gamma-delta T cell-based therapies for cancer.

Co-authors with Lamb for the Scientific Reports study, A combined treatment regimen of MGMT-modified T cells and temozolomide chemotherapy is effective against primary high grade gliomas, are Larisa Pereboeva and Samantha Youngblood, UAB Department of Medicine, Division of Hematology and Oncology; G. Yancey Gillespie, James M. Markert and Catherine Langford, UAB Department of Neurosurgery; L. Burton Nabors, UAB Department of Neurology; and Anindya Dasgupta and H. Trent Spencer, Emory University Department of Pediatrics, Atlanta, Georgia.

The UAB departments of Medicine, Neurology and Neurosurgery are part of the UAB Marnix E. Heersink School of Medicine. At UAB, Nabors holds the William Austin Brown Endowed Professorship in the ONeal Comprehensive Cancer Center.

Scientific Reports

Experimental study

Animals

A combined treatment regimen of MGMT-modified T cells and temozolomide chemotherapy is effective against primary high grade gliomas

26-Oct-2021

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Cancer-fighting spinoff from UAB grows through IPO, preclinical research results and a clinical trial - EurekAlert

Newswise New Brunswick, N.J., December 9, 2021 Research underway at Rutgers Cancer Institute of New Jersey will contribute to the development of new cancer treatments that are based on the administration of cancer-fighting immune cells to patients. This type of treatment is known as adoptive cell therapy. Healthy volunteers with no history of cancer are being sought to contribute blood cells that may be used in the development of cancer clinical trials.

The blood cells are collected through a procedure called apheresis in which blood is run through a machine that separates plasma and cells from the blood. The cells will be stored and used to manufacture adoptive cell transfer therapies as part of approved clinical trials and other clinical research that are separate from this study. The role of the healthy volunteer cells is to make the cancer-fighting immune cells collected from patients grow to large numbers in the laboratory so that they can be given as a cancer treatment.

Christian Hinrichs, MD, chief of the Section of Cancer Immunotherapy and co-director of the Duncan and Nancy MacMillan Cancer Immunology and Metabolism Center of Excellence at Rutgers Cancer Institute, is the principal investigator of the study. Adoptive cell therapy is a living treatment that harnesses the ability of immune cells to multiply and fight cancer in patients. This type of treatment is emerging as an effective, and sometimes curative, strategy for certain cancers that cannot be treated any other way. The availability of cells from healthy volunteers is crucial to ongoing development of these treatments and specifically to the generation of treatments for our patients participating in clinical trials at Rutgers Cancer Institute of New Jersey, notes Dr. Hinrichs, who is also a professor of medicine at Rutgers Robert Wood Johnson Medical School.

Individuals aged 18 and older who weigh at least 100 pounds are eligible to take part in the study. Other criteria also must be met. Prior to being accepted into the study, participants are required to undergo other tests including routine bloodwork and a physical exam.

Approximately 500 participants are being sought to take part in the study, which is available through Rutgers Cancer Institute. For more information on how to take part in this trial, individuals can email: [emailprotected].

About Rutgers Cancer Institute of New Jersey

As New Jerseys only National Cancer Institute-designated Comprehensive Cancer Center, Rutgers Cancer Institute, together with RWJBarnabas Health, offers the most advanced cancer treatment options including bone marrow transplantation, proton therapy, CAR T-cell therapy and complex surgical procedures. Along with clinical trials and novel therapeutics such as precision medicine and immunotherapy many of which are not widely available patients have access to these cutting-edge therapies at Rutgers Cancer Institute of New Jersey in New Brunswick, Rutgers Cancer Institute of New Jersey at University Hospital in Newark, as well as through RWJBarnabas Health facilities. To make a tax-deductible gift to support the Cancer Institute of New Jersey, call 848-932-8013 or visit http://www.cinj.org/giving.

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Exploring New Cancer Therapies that use a Patients Immune System to Fight Tumors - Newswise

Anthony Soyak is a self-described gym rat. Hes been doing CrossFit and lifting weights for years. But three years ago, he started feeling a pain in his shoulder.

He started with treatments like physical therapy, dry needling, and chiropractic visits. He saw some relief, but the pain would always reappear.

The pain started while he and his family lived in Milwaukee, Wisconsin. Eventually, he took his current job at Sanford Health, moving to Sioux Falls, South Dakota.

At Sanford, he met with orthopedic surgeon Jason Hurd, M.D. in March 2021, who told him some unexpected news.

We discovered that I had a partial rotator cuff tear in my left shoulder, said Soyak.

Soyak had two treatment routes. The first was surgery, where he would face over a year of recovery time.

The second was cell therapy.

Dr. Hurd recommended Soyak visit with Donella Herman, M.D., who does the cell treatment.

She answered all of my questions, and explained that its less invasive and has a quicker recovery time. That was the selling point for me, he said.

Learn more: Cell therapies at Sanford Health

BMAC treatment, or bone marrow aspiration concentrate, is the cell therapy Soyak received.

The same-day procedure takes bone marrow cells from an area of the body. Then, the concentration is separated, isolating the therapeutic cells. An ultra-concentrated BMAC dosage is then injected back into the site of injury, using an ultrasound to target the exact location, to expedite the healing process.

But, before the therapeutic cells are injected back into a patient, theyre rigorously tested to ensure safety and efficacy.

This meticulous nature is what separates Sanford Health from other health care providers who claim to offer cell therapy.

Soyak walked out the same day in a sling. Instead of a year, or possibly more, his recovery time was three weeks.

He periodically met with Dr. Herman, to see how the tear was responding to the therapy. Each time he went, they did an ultrasound.

Youd see the initial scans where there was a gap in the muscles, and actually see where the tear was. Then, she would compare that to where we were.

There is no more gap. Not only how I felt, but to actually see the progress was really cool, he said.

The more Soyak takes it slow, the stronger hes become.

I dont have any pain in my daily activities anymore. I dont wake up in pain. So, from a normal standpoint, I feel great, and Im starting to get more confident in the gym.

Posted In Orthopedics, Rehabilitation & Therapy, Research, Sioux Falls, Sports Medicine

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Workout warrior benefits from regenerative medicine - Sanford Health News

A new protein variant underlies the ability of gastric cancers to resist an otherwise effective family of chemotherapy drugs, according to a study by a multidisciplinary team at Weill Cornell Medicine. The results suggest a treatment strategy that could improve the prognoses of many patients with cancer.

The study, published Oct. 20 in Developmental Cell, and led by co-first authors, Drs. Prashant Thakkar and Katsuhiro Kita, former postdocs at Weill Cornell Medicine, combined clinical insight, laboratory experiments and sophisticated computational analysis to determine how some tumor cells resist a family of chemotherapy drugs called taxanes. Taxane treatment works by interfering with proteins that make up the cells internal skeleton, but the variant protein, called CLIP-170S, allows cancer cells to dodge that interference.

"We identified a novel variant that is clinically prevalent and is expressed in more than 60 percent of patients with gastric cancer and operates with a mechanism that's different from previously discovered ones," said co-senior author Dr. Paraskevi Giannakakou, professor of pharmacology in medicine and director of research in the Division of Hematology and Medical Oncology, and associate director for education in the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.

Taxanes, based on compounds originally discovered in yew trees, are first-line treatments for many cancers. Unfortunately, taxane-resistant cells often arise and survive the treatment, leaving patients with few options and poor prognoses. The problem is especially bad in gastric cancer.

"Most patients with gastric cancer live less than a year, and if we could figure out a way to make the taxanes more effective, we could have a bigger impact on patients," said co-senior author Dr. Manish Shah, director of the Gastrointestinal Oncology Program and chief of the Solid Tumor Oncology Service in the Division of Hematology and Medical Oncology at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center and the Bartlett Family Professor of Gastrointestinal Oncology and member of the Meyer Cancer Center at Weill Cornell Medicine. About 80 percent of gastric cancer patients develop taxane-resistant tumors, he said.

While years of research has revealed multiple ways cancer cells can resist taxane-mediated killing, those results have done little to change the clinical statistics.

"Everyone tries to understand mechanisms of taxane resistance, and yet nothing is helping patients clinically, none of the resistance mechanisms identified in the lab has made a clinical impact," Dr. Giannakakou said.

Wanting to take another stab at the problem, Dr. Shah approached Dr. Giannakakou with a reanalysis he'd done on data from the clinical trial that led to the FDA approval of taxanes for the treatment of patients with gastric cancer. The analysis revealed a subset of gastric cancer patients who didn't benefit at all from taxane treatment, suggesting that their tumors were drug-resistant even before being exposed to the compound.

The researchers, along with a multi-institutional team of collaborators, compared cells derived from taxane-resistant with those from taxane-sensitive tumors. They discovered that the taxane-resistant cells carried a variant form of a protein called CLIP-170, which normally helps the function of the cell's cytoskeleton.

Next, the team enlisted the aid of computational biologists to look for ways to overcome the newly discovered taxane resistance mechanism. Starting with a database of approved drugs, we created a computational program that was able to screen through these molecules, in silico, to identify the ones that would essentially make resistant cells look more like cells that are sensitive to taxanes," said co-senior author Dr. Olivier Elemento, director of the Caryl and Israel Englander Institute for Precision Medicine, associate director of the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine and a professor of physiology and biophysics at Weill Cornell Medicine.

The algorithm highlighted a surprising candidate: imatinib, a leukemia drug sold under the brand name Gleevec. Imatinib's known mechanism of action is completely unrelated to that of taxanes, while gastric cancer is not one of its clinical indications. Nevertheless, the researchers confirmed that a combination of the two drugs kills taxane-resistant tumors in lab dishes.

"That's important, because it demonstrates how you can go in without preconceptions and use computational screening to come up with molecules that have an effect," said Dr. Elemento, who is also a co-founder and equity stakeholder of OneThree Biotech, an artificial intelligence-driven drug discovery and development company.

Because imatinib is already an approved drug, the investigators hope to start clinical trials on the combined treatment soon. CLIP-170 variants could also serve as biomarkers for taxane resistance in many types of solid tumors. The whole story is really quite remarkable, and it opens the door for overcoming taxane resistance in other cancers as well, said Dr. Shah, who is also co-director of the Center for Advanced Digestive Care at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center.

Read more from the original source:
Protein Variant Identified that Renders Chemotherapy Ineffective in Gastric Cancer - Weill Cornell Medicine Newsroom

In patients with refractory B-cell lymphoma, thoracic imaging findings correlated with cytokine release syndrome grade following chimeric antigen receptor (CAR) T-cell infusion. This is according to a study published in Radiology which also showed that CAR T-cell therapy yielded high rates of imaging-based treatment response.

Imaging plays a critical role in the evaluation of clinical cytokine release syndrome and immune effector cellassociated neurotoxicity syndrome (ICANS) toxicity following CAR T-cell treatment, wrote Daniel Smith, M.D., a radiologist at the University Hospitals Cleveland Medical Center in Ohio. Specific findings at thoracic imagingin particular, pleural effusion and atelectasismay prove useful correlates for severe clinical grades of cytokine release syndrome, while findings related to ICANS tend to be less specific and less frequent.

CAR T-cell immunotherapy is increasingly used for refractory lymphoma, but it may lead to cytokine release syndrome and ICANS in the early period following infusion. The associations between cytokine release syndrome or ICANS grade and imaging findings are not established. The goal of this study was to characterize thoracic and neuroimaging findings associated with cytokine release syndrome and ICANS in patients with refractory B-cell lymphoma.

The retrospective analysis included 38 patients (mean age 59; 61% men) with refractory B-cell lymphoma who underwent CAR T-cell infusion. Of these, 63% and 29% experienced clinical grade 1 or higher cytokine release syndrome and ICANS, respectively. Patients with grade 2 or higher cytokine release syndrome were more likely to have thoracic imaging evidence at radiography, CT and/or MRI of pleural effusions (36% vs 8.3%, P = .04) and atelectasis (57% vs 25%, P = .048) than patients without cytokine release syndrome or with grade 1 toxicity. Positive imaging findings were identified in 43% with grade 2 or higher ICANS who underwent neuroimaging. Patients undergoing CAR T-cell therapy had higher rates of clinical response, including 56% with complete response and 19%with partial response.

Our findings further highlight the central role of PET/CT in disease response after CAR-T cell therapy, the authors wrote.

Limitations of the study included its retrospective design, small sample size, and that most patients without toxicity did not undergo imaging.

In an accompanying editorial, Mark Langer, M.D., professor of clinical radiation oncology at Indiana University School of Medicine, wrote that in the study by Smith et al, atelectasis and pleural effusions were more common in patients with severe cytokine release syndrome than in those with mild or absent cases. Edema and airway consolidation were not more common. He added, Whether such features emerge only when the case becomes clinically more severe or whether these features are early signs of disease that will eventually evolve into a higher-grade condition is a question deserving of future study.

As more data are prospectively obtained, imaging guidelines to better monitor for the important conditions examined here may be established, and the information collected used to effectively intervene early in detection and treatment, Dr. Langer wrote.

The rest is here:
Imaging Findings May Help Detect CAR T-Cell Therapy Toxicities - Diagnostic Imaging

STAFFORD, Texas--(BUSINESS WIRE)--Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the Company), a clinical-stage biopharmaceutical company focused on the development of GP2, an immunotherapy to prevent breast cancer recurrences in patients who have previously undergone surgery, today announced the publication of a poster for the GP2 Phase IIb clinical trial at the San Antonio Breast Cancer Symposium 2021 (SABCS). The CEO of Greenwich LifeSciences, Snehal Patel, recorded an audio track providing an overview. The abstract can be viewed at the bottom of this press release. The full poster with figures, tables, and audio can be accessed or downloaded from the Companys website here.

Figure 1 is the new data published yesterday evening at SABCS, which shows that GP2 immune response at baseline could be a prognosticator of cancer recurrence. The Phase IIb clinical trial enrolled HER2 positive patients, who received a standard course of trastuzumab after surgery, and HER2 low patients, who did not receive trastuzumab after surgery. A Delayed-Type Hypersensitivity (DTH) reaction was used to assess baseline in vivo immune responses to GP2 in patients prior to exposure to GP2 treatment or placebo.

The poster data can be summarized as follows:

It was observed that 22.8% or 33 patients of the 145 patients reacted to GP2 at baseline with a positive immune response, which is defined as an induration of 5 mm or greater in the baseline DTH test.

Of the 33 patients who did have a positive baseline DTH immune response to GP2, 8 patients recurred, which is a recurrence rate of 24.2% over 5 years of follow up, with a median time to recurrence of 99 days (0.27 years).

Of the 77.2% or 112 patients who did not have a positive DTH baseline immune response to GP2, 14 patients recurred, which is a recurrence rate of 12.5% over 5 years of follow up, with a median time to recurrence of 438 days (1.2 years).

Mr. Patel commented, This new GP2 specific T cell data suggests that patients with a positive baseline immune response to GP2 recurred twice as fast and approximately 7 to 11 months sooner than those without a positive baseline immune response did. While this data is very promising, the number of recurrences are low, thus we need to further confirm these observations in the upcoming Phase III clinical trial to determine if they are statistically significant. To further diversify our pipeline, we plan to fully characterize GP2 specific T cells by sequencing the DNA of the T cells at baseline and after treatment with GP2 to assess how these T cells change over time and if they can be developed into CAR-T drug candidates. Expansion into GP2 specific CAR-T cells could potentially become another platform technology to complement GP2 peptide treatment in higher risk patients. We expect new T cell data from the Phase III trial to become available in 2022.

Today is the one year anniversary of the Companys SABCS 2020 poster, which became the basis for Figure 2. This figure summarizes the efficacy, immune response, and safety Phase IIb data presented over the past year. The Kaplan Meier analysis for HER2 positive patients treated with GP2 immunotherapy shows 100% disease free survival (0% breast cancer recurrences, p = 0.0338) following surgery and Herceptin treatment over median 5 years of follow-up. These patients completed the Primary Immunization Series (PIS) which led to peak immunity at 6 months. No serious adverse events attributable to GLSI-100 were observed. Figure 1 and Figure 2 summarize all of the 5 year GP2 data published to date.

SABCS Abstract P2-13-29:

Title: Analysis of GP2 immune response and relationship to recurrence in a prospective, randomized, placebo-controlled, single-blinded, multicenter, phase IIb study evaluating the reduction of recurrences using HER2/neu peptide GP2 (GLSI-100) vs. GM-CSF alone after adjuvant trastuzumab in HER2 positive women with operable breast cancer

Snehal S Patel, David B McWilliams, Mira S Patel, Christine T Fischette, Jaye Thompson and F Joseph Daugherty.

Greenwich LifeSciences, Stafford, TX

Background: Delayed type hypersensitivity (DTH) skin tests in the randomized, active-controlled, single-blinded, multicenter Phase IIb trial investigating GLSI-100 (GP2+GM-CSF) administered in the adjuvant setting to node-positive and high-risk node-negative breast cancer patients with tumors expressing any degree of HER2 (immuno-histochemistry [IHC] 1-3+) (NCT00524277) have been analyzed. The trial enrolled HLA-A*02 patients randomized to receive GLSI-100 versus GM-CSF alone. The trial's primary objective was to determine if treatment with GLSI-100, a HER2-derived peptide, reduces recurrence rates. Analyses for this trial showing GLSI-100 to be efficacious, safe and immunogenic have been previously reported by Patel et al. and Mittendorf et al.

Methods: Consented patients were randomized and scheduled to receive GLSI-100 (500 mcg GP2: 125 mcg GM-CSF) or control (GM-CSF only) via 6 intradermal injections every 3-4 weeks as part of the Primary Immunization Series (PIS) for the first 6 months and 4 booster intradermal injections every 6 months thereafter. Boosters were introduced during the trial, thus some patients did not receive all 4 boosters. DTH skin tests were assessed at baseline and after the 6th dose with the orthogonal mean of each skin reaction measured 48-72 hours after injection using the sensitive ballpoint-pen method.

Results: The study enrolled 180 patients across 16 clinical sites with both HER2 3+ positive and low HER2 expressors (1-2+). After 5 years of follow-up, the Kaplan-Meier estimated 5-year DFS rate in the 46 HER2 3+ patients treated with GLSI-100, if the patient completed the PIS, was 100% versus 89.4% (95% CI:76.2, 95.5%) in the 50 placebo patients treated with GM-CSF (p = 0.0338). GLSI-100 was shown to be well tolerated with no SAEs deemed related to study medication and elicited a potent immune response measured by local skin tests and immunological assays. Injection site reactions were common, occurring in almost 100% of patients treated with either GLSI-100 or GM-CSF alone. Previous publications have reported the increase in DTH response reported among patients after treatment with GLSI-100. However, it was of interest to understand the positive DTH responses to GP2 noted at baseline. 22.8% of patients reacted to GP2 at baseline with induration of 5mm or greater. In the subgroup of patients who later experienced a breast cancer recurrence, 36.4% (8/22) had such a baseline response. Analysis of the time to recurrence among those recurring found that the median time to recurrence was 0.6 years for those with a baseline response while those that did not have a positive baseline DTH response to GP2 took 1.2 years to recur.

Conclusions: This study demonstrated that GLSI-100 safely elicited a potent immune response as evidenced by increased DTH skin responses with treatment paired with improved disease-free survival. It is theorized that a positive baseline DTH skin test to GP2 may be evidence of an existing immune response to GP2 associated with residual disease, impending recurrence, or prior treatments. Further studies assessing if GP2 immune response is an important prognosticator of cancer disease state or recurrence are planned.

About SABCS

The 44th annual SABCS has grown to be the industrys premier breast cancer conference for basic, translational, and clinical cancer research professionals. It is well-known for presenting the latest breast cancer data from all over the world. More than 7,500 health care professionals from more than 90 countries attend annually. Baylor College of Medicine became a joint sponsor of SABCS in 2005. The Cancer Therapy & Research Center at UT Health Science Center San Antonio and American Association for Cancer Research began collaborations with SABCS in 2007. For more information, please visit the conference website at: https://www.sabcs.org/

About FLAMINGO-01 and GLSI-100

The Phase III clinical trial will be called FLAMINGO-01 and the combination of GP2 + GM-CSF will be called GLSI-100. The Phase III trial is comprised of 2 blinded, randomized, placebo-controlled arms for approximately 500 HLA-A*02 patients and 1 open label arm of up to 100 patients for all other HLA types. An interim analysis has been designed to detect a hazard ratio of 0.3 in IDFS, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater. The trial is currently being registered on clinicaltrials.gov and the link and trial identifier will be published shortly. For future updates about FLAMINGO-01 please visit the Companys clinical trial tab at https://greenwichlifesciences.com/clinical-trials/.

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 282,000 new breast cancer patients and 3.8 million breast cancer survivors in 2021. HER2/neu (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.

About Greenwich LifeSciences, Inc.

Greenwich LifeSciences is a clinical-stage biopharmaceutical company focused on the development of GP2, an immunotherapy to prevent breast cancer recurrences in patients who have previously undergone surgery. GP2 is a 9 amino acid transmembrane peptide of the HER2/neu protein. In a randomized, single-blinded, placebo-controlled, multi-center (16 sites led by MD Anderson Cancer Center) Phase IIb clinical trial, no recurrences were observed in the HER2/neu 3+ adjuvant setting after median 5 years of follow-up, if the patient received the 6 primary intradermal injections over the first 6 months (p = 0.0338). Of the 138 patients that have been treated with GLSI-100 to date over 4 clinical trials, treatment was well tolerated and no serious adverse events were observed related to the immunotherapy. Greenwich LifeSciences is planning to commence a Phase III clinical trial using a similar treatment regime as the Phase IIb clinical trial. For more information on Greenwich LifeSciences, please visit the Companys website at http://www.greenwichlifesciences.com and follow the Company's Twitter at https://twitter.com/GreenwichLS.

About GP2 Immunotherapy Immune Response

As previously reported, GP2 immunotherapy generated GP2-specific immune responses, leading to no metastatic breast cancer recurrence in the HER2/neu 3+ population in the Phase IIb clinical trial, thus supporting GP2s mechanism of action. Statistically significant peak immunity was reached after 6 months of GP2 treatment, as measured in both the Dimer Binding Assay and the DTH skin test. HER2/neu 3+ population immune response was similar to the HER2/neu 1-2+ population immune response, suggesting the potential to treat the HER2/neu 1-2+ population (including triple negative breast cancer) with GP2 immunotherapy in combination with trastuzumab (Herceptin) based products and other clinically active agents. The broad based immune response suggests the potential for GP2 to treat other HER2/neu 1-3+ expressing cancers. For more information on GP2 immune response and clinical data, please visit the Companys clinical trial tab at https://greenwichlifesciences.com/clinical-trials/.

Forward-Looking Statement Disclaimer

Statements in this press release contain forward-looking statements that are subject to substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this press release are forward-looking statements. Forward-looking statements contained in this press release may be identified by the use of words such as anticipate, believe, contemplate, could, estimate, expect, intend, seek, may, might, plan, potential, predict, project, target, aim, should, "will, would, or the negative of these words or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements are based on Greenwich LifeSciences Inc.s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict, including statements regarding the intended use of net proceeds from the public offering; consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are described more fully in the section titled Risk Factors in the final prospectus related to the public offering filed with the SEC. Forward-looking statements contained in this announcement are made as of this date, and Greenwich LifeSciences, Inc. undertakes no duty to update such information except as required under applicable law.

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Greenwich LifeSciences Announces Presentation of 5 Year Data for GP2 Phase IIb Clinical Trial, Revealing Potential For New T Cell Platform Technology...

Adicet Bio today sharedpositive interim results from its Phase I study on a potential treatment for B-cell Non-Hodgkin's Lymphoma.

ADI-001, an investigational allogeneic gamma delta CAR T cell therapy, generated positive early responses from three of four evaluable participants, two of whom achieved complete responses (CR) while one had a partial response (PR) that researchers logged as "near complete."

As of the November 22 cutoff, six patients had been enrolled in the trial, though two did not reach the 28th day and were considered not evaluable to test the drug's efficacy. All participants had already received a median of five lines of systemic therapy prior to the trial.

One patient who had already gotten autologous CD19 CAR T therapy reported CR after a single infusion of the drug at the lowest dose. Of the four evaluable patients, three received ADI-001 at a level one dose, or 30 million CAR+ cells, while the fourth was given a level-two dose at 100 million CAR+ cells. Of the three who achieved PR or better, one had diffuse large B-cell lymphoma with five prior lines of therapy, one had follicular lymphoma that turned into a large B-cell tumor with four prior lines, and the third was diagnosed with mantle cell lymphoma with five prior lines of treatment.

ADI-001 works by targeting malignant B-cells through an anti-CD20 CAR and gamma delta innate and T-cell endogenous cytotoxicity receptors. In preclinical models, gamma delta T cells engineered with anti-CD20 CAR showed positive antitumor activity. So far, all the infusions were well-tolerated, with no reports of graft vs host disease, dose-limiting toxicities, grade 3 or higher cytokine release syndrome, and immune effector cell-associated neurotoxicity syndrome. This suggests a wide therapeutic potential for ADI-001.

"The preliminary safety and efficacy data from low-dose ADI-001 collected to date indicate the potential for a broad therapeutic window. Without the need for gene editing and its associated safety concerns, our platform is designed to preserve the natural innate and adaptive anti-tumor activity of gamma delta CAR T cells, which we believe may lead to better durability," said Francesco Galimi, M.D., Ph.D., the senior vice president and chief medical officer of Adicet Bio, in a statement.

The trial is still in its early stages and is expected to enroll around 75 patients. The primary objectives are to determine the drug's tolerability, safety, pharmacodynamics, and pharmacokinetics. The research also intends to find out the optimal dosing if it is used as monotherapy. Details of the study are available with the U.S. National Library of Medicine.

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In approaching the end of another full year within the COVID-19 pandemic, there's still much being learned about the dangerous respiratory virus that has seized the world. Developments in the last 12 months include greater confirmation that wearing masks do help to stop the spread, the virus can affect even the healthiest individuals long-term, and the first available vaccines offer extensive, but not complete, protection.

For certain populations, the protection offered by receiving a vaccine is even more limited. This year, rheumatologists found this to be the case for their patients who are on immunosuppressants or immunomodulatory treatmentsa realized concern 1 year after learning the severity by which immunosuppressed patients can be affected by COVID-19.

An array of studies have been performed in hopes of gaining a better understanding on this topic. The research revealed some great insight, but an important takeaway was that patients who are on immunosuppressants or immunomodulatory treatments still benefit from receiving the vaccine, even if it's not as effective as it is in the general population.

Earlier this year, Ruth Fernandez-Ruiz, MD, MS, Division of Rheumatology, Department of Medicine, New York University Grossman School of Medicine, conducted a study that evaluated the immune response and disease status in patients with systemic lupus erythematosus (SLE) which was presented at the American College of Rheumatology 2021 Convergence.

In an interview with HCPLive, Fernandez-Ruiz explained that all the phase 3 trials that were performed for the COVID-19 vaccines excluded patients who were taking immunosuppressants or immune-modifying drugs within 6 months from the time of enrollment.

At the time we initiated the study, Fernandez-Ruiz said, the data on rheumatic disease patients was virtually absent.

Previous research looked at this phenomenon with other vaccines, like the flu vaccine, and found that taking immunosuppressants did impact vaccine efficacy.

Prior to this study, Fernandez-Ruiz also collaborated on research that examined antibody responses in patients with lupus who had natural infection of SARS-COV-2.

We found that most patients were able to generate and maintain an antibody response after COVID-19 disease, Fernandez-Ruiz said. So overall, it wasnt really clear how our patients were going to respond to the COVID-19 vaccine, and there was a real need to study rheumatic disease patients.

Charalampos Papagoras, MD, PhD, Assistant Professor of Rheumatology at Department of Medicine, Democritus University of Thrace, led research on the outcomes of COVID-19 in vaccinated patients compared with unvaccinated patients who have systemic rheumatic diseases.

His study concluded that the severity of breakthrough COVID-19 cases depended on the vaccination status of the patient.

Aside from vaccination status, there were no differences in demographics, systemic rheumatic disease type, treatment or comorbidities between the 3 groups. However, hospitalization and mortality rates were higher in the unvaccinated group (29.3% and 4.1%, respectively), even when compared with the partially vaccinated group (21% and 0%).

Of course, patients who were fully vaccinated had the best outcome when faced with a COVID-19 breakthrough infection (10.3% and 0%).

The CDC was unclear if there were any disease-specific factors that could play a role in vaccine responses, Fernandez-Ruiz mentioned. Therefore, the team of investigators were compelled to focus particularly on the lupus population.

Their results showed approximately 30% of patients with lupus had a decrease in COVID-19 antibody responses and microneutralization titers compared to controls. Additionally, a correlation was found between circulating antibody levels against the spike protein and interfering gamma production by immune cells.

A low vaccine response was defined as less than or equal to 100 units per ml, which is the lowest value seen in controls.

After a patients vaccine response level was defined, the investigators further compared the 26 lupus patients who had a low response to the 64 lupus patients who had adequate response.

We found that a normal anti-double stranded DNA antibody, and taking any immunosuppressant medication, other than antimalarials like hydroxychloroquine, were associated with a decreased vaccine response, Fernandez-Ruiz said,

This particular study she led didnt have a large enough sample size to look at the effect of each individual medication, but Fernandez-Ruiz emphasized that research in this area has grown.

We do know now, she said, that other studies have shown that medications like methotrexate, mycophenolate mofetil, B-cell depleting agents like rituximab, and systemic steroids are likely playing a major role in blunting antibody response to the vaccine.

A study led by Jean Liew, MD, MS, Assistant Professor, Rheumatology, Boston University School of Medicine, found that most of the patients with rheumatic disease who had to be hospitalized for COVID-19, despite being vaccinated, were the patients taking B-cell depletion therapy medication.

The results of the trial, SARS-COV-2 Infections Among Vaccinated Individuals with Rheumatic Disease: Results from the COVID-19 Global Rheumatology Alliance Provider Registry, noted that of the 87 fully-vaccinated patients with rheumatic disease, 22 of them had breakthrough cases so severe they needed to be hospitalized.

Liew said in an interview with HCPLive that these results werent exactly surprising because they were in line with other laboratory-based studies she read.

While the findings are meaningful, the other side to these data are equally enlightening. B-cell depleting medications like rituximab, and antimetabolites like mycophenolate appeared as treatments in the hospitalized group, but what about the treatment options that were absent from this group?

Overall, the results should be reassuring, Liew explained, that other medication classes that are immunomodulatory that we use for rheumatic disease patients, like TNF inhibitors and other biologics that target specific cytokines, theyre not really represented in the people who were hospitalized after they were fully vaccinated.

For the highest risk patients, its imperative to continue to look at other prophylactic strategies pre or post exposure, like monoclonal antibodies or the potential antiviral oral medication, according to Liew.

Patients in this particular high-risk population, and the providers that treat them, have to walk a thin line.

For them, the only option for treatment is ultimately limited to the immunomodulatory or immunosuppressive medication that leaves them vulnerable to a breakthrough COVID-19 infection.

Adjusting or switching to another treatment simply wouldnt be effective at maintaining control of the disease and would then leave the patient vulnerable to a disease flare, which in turn could lead to poor outcomes if they were to be infected with COVID-19.

Theres not really an alternative therapy for these people, Liew said, which makes the implication here that we need to think about what other things we can do in addition to vaccinating them.

Fernandez-Ruizs study monitored for disease flare and found that 11% of vaccinated patients had a lupus flare.

Only 1 of these patients had a severe flare, she explained, which means that this was overall rare, and these findings really support the safety of the COVID-19 vaccine in patients with lupus.

The line may be thin, but it can be walked.

The American College of Rheumatology continuously updates their guidelines surrounding the COVID-19 vaccines with new data that arise. They recommend withholding most immunosuppressant medications after vaccination for a period of time.

Fernandez-Ruiz emphasized that these are guidelines, and rheumatologists have to make individualized decisions with each patient. The patients disease, the medication theyre on, the disease activity at the time, are all factors that need to be considered when discussing this with a patient.

Ive encountered situations where the disease activity, or the specific manifestations were treating, theyre life-threatening or theyre organ-threatening, so we cant have the luxury of just simply holding the medication, she said.

Its a process to be taken step-by-step. And Fernandez-Ruiz is already working on the next one.

Along with a team of investigators, Fernandez-Ruiz said she is currently studying the frequency and severity of breakthrough infections.

We also need to better understand whether holding immunosuppressants post-vaccination, and administering an additional dose of the vaccines, actually leads to improved humoral and cellular immunity to these vaccines, she said.

Even though approximately 30% of patients showed a relatively low response, we dont know if that response is enough to protect them from very poor outcomes of COVID-19. We think about infection prevention in general as an ideal outcome but also preventing hospitalization, oxygen requirement, ICU admission, intubation, these are all great things that we should aim for.

This year, we have certainly expanded our knowledge and understanding on the various ways COVID-19 has affected our lives and were on the path to continue doing so.

You can see it either way, Fernandez-Ruiz said. We saw 30% of patients had a low-vaccine response, but 70% of patients had a pretty good response, and this is without the booster or third dose shot, the additional dose that were recommending now, so thats actually pretty good.

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Rheumatologists Navigate Treatment Plans in the Era of COVID-19 Vaccines - MD Magazine