Category Archives: Cell Therapy

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Adaptimmune Therapeutics plc (Nasdaq: ADAP), a leader in T-cell therapy to treat cancer, today announced that it has initiated its study of NY-ESO SPEAR Tcells targeting NY-ESO in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 inhibitor marketed by Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the US and Canada), in patients with multiple myeloma. This study is now open for enrollment.

This is Adaptimmunes third clinical trial to initiate within the past month. The Company recently announced the initiation of clinical studies with its wholly-owned SPEAR T-cells targeting AFP in hepatocellular carcinoma, as well as its wholly-owned SPEAR T-cells targeting MAGE-A4 in seven malignant solid tumors.

We are excited to initiate this study as we have already seen encouraging data in a previous singleagent study of NYESO SPEAR T-cells in patients with advanced myeloma in the context of stem cell transplantation, said Rafael Amado, Adaptimmunes Chief Medical Officer. KEYTRUDA has also shown preliminary evidence of activity in multiple myeloma in combination, and there is preclinical evidence to support the view that the combination of NY-ESO SPEAR T-cells and anti-PD-1 therapy may lead to meaningful antitumor activity.

This is an open-label, randomized pilot study designed to evaluate the safety and anti-tumor activity of Adaptimmunes NY-ESO therapeutic candidate alone or in combination with KEYTRUDA in patients who are HLA-A*02 positive and have relapsed and refractory multiple myeloma expressing NY-ESO-1 and/or LAGE1a. The study will enroll up to 20 patients. The primary objective of the study is to evaluate the safety and tolerability of NY-ESO SPEAR T-cell therapy alone or in combination with KEYTRUDA. Additional objectives include antitumor activity, persistence of genetically modified cells in the body, and evaluation of the phenotype and functionality of genetically modified cells isolated from peripheral blood or tumor post infusion.

Adaptimmune is developing the NY-ESO SPEAR T-cell program under a strategic collaboration agreement with GSK.

Clinical Trial Collaboration Agreement for use of KEYTRUDA

Adaptimmune has a clinical trial collaboration agreement with Merck & Co., Inc., Kenilworth, NJ, USA for the use of KEYTRUDA in this study. The agreement is between Adaptimmune and Merck & Co., Inc., Kenilworth, NJ, USA, through a subsidiary. Under the agreement, the trial will be sponsored by Adaptimmune. The agreement also includes provision for potential expansion to include Phase III registration studies in the same indication. Additional details were not disclosed.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

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Adaptimmune Therapeutics (ADAP) Begins Study to Evaluate ... - StreetInsider.com

TolerogenixX has proved that it can get rid of immunosuppressants in organ transplants in Phase I and secured seed funding from High-Tech Grnderfonds.

TolerogenixXis a startup from the Heidelberg University Hospital that developspersonalized immunosuppression therapies. Its cell therapy technology has just passed Phase I, where it showed an impressive efficacy in preventing the rejection of kidney transplants without the need for immunosuppressive drugs.

The promising results seemto have convinced the German life sciences investorHigh-Tech Grnderfonds (HTGF),from which TolerogenixX has secured seed funding. HTGF is the first investor to jump in after pre-seed financing from the German Government. The funds, of an undisclosedamount, will help the startup make the preparations for a Phase II trial, planned for spring 2018.

TolerogenixXstechnology provides individualized immunosuppression, tailored specifically to the donor tissue. To do so,peripheral blood mononuclear cells (PBMCs) are harvested from the donor and treated with mitomycinCand then infused into the patient prior to the transplant.

Researchers at the University of Heidelberg discovered that mitomycin C inducesa change of behavior in dendritic cells, leading them to suppressT-cell responses. Immunological tests conducted during the trial revealed that the recipients had developed tolerance towards the donor.

The TolerogenixX technique represents a milestone in the field of individualized immunosuppression, saidPhilipp Rittershaus, Investment Manager at HTGF. Indeed, the therapy would allow transplantation without the need for immunosuppressants, which carry many severe side effects and leave patients completely unprotected against infections.

If everything goes well,TolerogenixX expects to complete Phase III andfile for approval in 2022. In addition, it will start a second program next year to treat autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus. The methodology would be very similar, just using autologous cells instead for the mitomycin C treatment instead of donor cells.

This is a real quantum leap in the treatment of transplant patients, said in a statement Matthias Schaier, CEO of TolerogenixX. In the future, it will no longer be necessary to take various medications with numerous side effects.

Images via crystal light / Shutterstock;TolerogenixX

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Seed Funding for a German Cell Therapy to Prevent Transplant ... - Labiotech.eu (blog)

NC

Yet today the 59-year-old father of two is planning a dream family trip to South Africa, something that would have been unthinkable a mere nine months ago.

The reason for this remarkable transformation is that last September Gordon, who suffered from severe heart failure after a series of heart attacks, underwent revolutionary stem cell therapy to repair the diseased muscle tissue in his heart.

I couldnt walk up the stairs without having stabbing pains in my heart and burning in my lungs. Sometimes I had to crawl for the last few steps.

I felt so low and helpless, says Gordon, who is married to Joanne, 50, and lives in Thorneholme, East Yorkshire.

Within a week of the operation I could climb the stairs again. Small things like that have made a huge difference to my life.

More than a million people in the UK suffer from heart disease. The general term for heart disease is cardiomyopathy, a condition in which the walls of the heart chambers have become stretched, thickened or stiff.

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This affects the hearts ability to pump blood around the body. Some types of cardiomyopathy are inherited and it can affect children and younger people.

I couldnt walk up the stairs without having stabbing pains

Gordon Foster

In others, lifestyle factors such as smoking, an unhealthy diet or a sedentary lifestyle can be to blame. There is no cure and although it can be treated with drugs such as ACE inhibitors, they often have side effects and arent a permanent solution.

In Gordons case his condition was the result of a series of heart attacks, the first of which struck when he was 30.

I woke up one morning feeling horribly sick so I ran to the bathroom. I was banging my head on the floor to try to get rid of the pain in my chest, he recalls. Everybody thought I was a goner because it was such a massive heart attack.

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10 Step plan to eliminate your risk of heart disease

Joanne and I got married two months later because she was worried I might not live until our wedding date.

However he did survive and he and Joanne went on to have two children, James, now 26, and Rebekah, 24. Then when James was just a year old Gordon had another heart attack and three years later, aged 37, he suffered a third.

He was diagnosed as suffering from heart failure which most commonly occurs following a heart attack when the heart muscle suffers irreparable damage.

Symptoms can include fatigue, shortness of breath and swelling. In severe cases people with heart failure are left unable to perform ordinary, day-to-day activities such as walking upstairs or are left breathless even when resting.

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By 2012 Gordons heart was functioning at just 17 per cent and he had been forced to retire on heart attack and three years later, aged 37, he suffered a third. from heart failure which most commonly occurs following a heart attack when the heart muscle suffers irreparable damage.

Symptoms can include fatigue, shortness of breath and swelling. failure are left unable to perform ordinary, day-to-day activities such as walking upstairs or are left breathless even when resting.

Functioning at just 17 per cent and he had been forced to retire on medical grounds from his job overseeing welding and fabricating sites.

For severely affected patients a heart transplant can be the only option but the chances of failure are high. Around 10 per cent of transplant patients die within a year of the operation and 25 per cent die within five years.

The need for treatment in this field has never been greater, says Professor Anthony Mathur, consultant cardiologist at St Bartholomews Hospital, London.

Now stem cell therapy is offering new hope to desperate patients and their families. The procedure involves extracting stem cells from bone marrow in the spine and injecting them into the heart.

Researchers hope that the stem cells, which are unique because they can grow into any type of body tissue, will grow into healthy heart cells and take over the work of the diseased or damaged ones.

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The procedure takes about 20 minutes and patients can usually go home the following day. Gordon became the first man in the UK to be offered the operation under the Compassionate Treatment Programme funded by the Heart Cells Foundation charity at St Bartholomews Hospital after his doctor put him forward to take part in a trial.

The charity has so far raised more than 6.5million to fund the Stem Cell Research Programme and is campaigning to raise further cash to treat thousands more patients.

Stem cell therapy is still in the development and research stage and the Compassionate Treatment Programme is funded purely by the Heart Cells Foundation charity, says its chairman Jenifer Rosenberg.

To treat one person costs 10,000 so we need the continued support of our donors to save lives.

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Queen Elizabeth II visits a ward during a tour of Great Ormond Street Hospital for sick children, 23rd July 1952

The treatment is currently in the second phase of clinical trials and phase three will start once funding is secured. If this is successful it is hoped that the treatment could eventually be offered on the NHS.

Gordon says he and his family will be forever thankful to the Heart Cells Foundation and his medical team at St Bartholemews for saving his life.

Without them, I believe I wouldnt be here today, he says. Im now able to lead a near-normal life and Im enjoying every moment I spend with my wife and children. I now live every day with hope.

Visit heartcellsfoundation.com

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How a revolutionary stem cell treatment could save your heart - Express.co.uk

BENGALURU:Full-fledged treatment for cancer and bone-related ailments using stem-cell within the state could soon be a possibility if a plan of a world renowned surgeon from the state succeeds.

Dr A A Shetty is a highly decorated orthopedic surgeon and professor based in the UK who won the Nobel equivalent of surgery called the Hunterian Medal, this year. In his aim to bring about next level cancer and orthopedic treatment, he has already set up two big stem cell research labs - one in Dharwad and another in Mangaluru, a few years back at a cost of around 20 to 25 crore. A hospital that will treat stem-related ailments has also been envisaged at a total cost of around Rs 200 to 250 crore.

Setting up the labs is part of a three-step goal. After setting up the labs, the next step will be producing the stem cells, whether it be for bone ailments, treatment for cervical cancer etc. Then the third step will be the application of these stem cells through our hospital or through tie-ups with other hospitals. I have already received the funding for setting up the hospital, says Dr Shetty in an interaction with CE in Bengaluru. He is originally from a small village called Asode in Udupi district.

The lab in Dharwad is located at SDM College and is being backed by Shri Dharmasthala Manjunatheshwara and will be primarily working on blood cancer and thalassemia treatment. The one in Mangaluru is located at K.S. Hegde Medical Academy (KSHEMA) and is backed by the NITTE group. It will work on cartilage and bone fracture treatments.The effort is no doubt for profit. We will charge the rich but the poor will be treated for free at our hospital, he says.

Already, Shetty has recruited a number of top stem cell researchers from the state who are presently abroad. I have recruited researchers who were doing their postdoc studies in Japan, South Korea. Presently there are four of them working at the two labs, he says. Shetty ultimately wants to settle in Karnataka and hopes to achieve his goal by 2020. The third stage of his plan also requires expertise in various cutting edge technologies such as robotics, computing and he will also be recruiting people who specialize in these fields.

Cancer Vaccination

Shetty also hopes to make cancer vaccination a possibility. Giving an example of cervical cancer, Shetty says, Few cancers can be vaccinated. Cervical cancer, one of the most rampant cancers, is one of them. We will use stems derived from iPS cell. In the UK, the vaccine cost 60 pounds. Our aim is to develop it and sell it at a very low cost, as low as Rs 100, he adds. Induced Pluripotent Stem Cells or iPS Cells are derived from the blood and skiwwn cells and can be reprogrammed to provide an unlimited source of any type of human cell.

Stem cells for Arthritis In 2013, Shetty devised a minimally invasive procedure to treat arthritis using stem cells. When the cartilage between the bones begin to erode, the bones rub against each other and cause severe pain. Shetty treated a patient suffering from knee arthritis. He drilled a hole into the patients knee bone and released stem cells that could grow into the cartilage. In all, the procedure lasted just 30 minutes. Shetty has already done as many as two dozen such procedures in India.

Trauma Center Shetty also says that he wants to develop and provide integrated trauma services. If a patient survives the golden hour then he/she can be saved. Majority die in the first hour of trauma. My integrated services will have specialized suits that will help reduce blood loss and will have other know-how. I am negotiating with the International Rotary on this, he adds. This may be established either in Mangalore or Bangalore.

Dr Vishal Rao, head and neck oncology surgeon at HCG Hospitals says that stem cells research is in the mid-stage of development and has great potential to grow in India. The IT and BT ministry is already taking great steps by encouraging startups on these lines, starting various schemes, he says. Vishal also pointed out that a number of private organizations, hospitals and individuals like those like Dr Shetty are also investing in the field.

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Stem-cell therapy for cancer comes closer home - The New Indian Express

"At StemGenex, we are committed to helping people achieve optimum health and better quality of life through the healing benefits of their own stem cells," said Alexander. "Specifically, we use adipose-derived adult stem cell therapy for patients battling conditions such as Multiple Sclerosis, Parkinson's disease, COPD, Rheumatoid Arthritis and Osteoarthritis. We are also committed to the science of stem cell therapy and sponsor five clinical outcome studiesregistered with theNational Institute of Health (NIH) for these diseases."

"What I personally witnessed before the start of StemGenex were patients who had exhausted conventional medical treatments but wanted to try alternative therapies. I was one of them, suffering from severe Rheumatoid Arthritis. Ihad only three options; I could seek a clinical trial, travel to outside of the U.S. to try alternative therapies such as stem cell treatment or petition the FDA for access to drugs under the agency's "expanded access," or "compassionate use" program. Now, new state laws, built on model legislation from the Goldwater Institute in Arizona, will potentially allow doctors and patients to make their own informed decisions on treatments that have cleared the safety phase of FDA testing."

Last year, in a move that was seen by some as a response to "Right to Try" laws, the 21st Century Cures Act, a landmark piece of legislation focused on medical innovation and medical research, was signed into law by President Obama. This Act provides the FDA with the flexibility to accelerate how it evaluates regenerative medicine treatments, such as stem cell therapies, while maintaining its high standards of safety and efficacy.

"We're on the cusp of a major change on how patients can access stem cell therapy," saidAlexander. "Today, new treatments and advances in research are giving new hope to people affected by a wide range of autoimmune and degenerative illnesses," said Alexander. "StemGenex Medical Group is proud to offer the highest quality of care and to potentially help those with unmet clinical needs improve their quality of life."

ABOUT StemGenex Medical Group StemGenex Medical Group is committed to helping people achieve optimum health and better quality of life through the healing benefits of their own stem cells. StemGenex provides stem cell therapy options for individuals suffering with inflammatory and degenerative illnesses. Committed to the science and innovation of stem cell treatment,StemGenex sponsors five clinical outcome studiesregistered with theNational Institutes of Health ("NIH") for Multiple Sclerosis, Parkinson's Disease, Rheumatoid Arthritis, Chronic Obstructive Pulmonary Disease ("COPD") and Osteoarthritis. These have been established to formally document and evaluate the quality of life changes in individuals following adipose-derived stem cell treatment.

Contact: Jamie Schubert, Director of Media & Community Relations jschubert@StemGenex.com, (858) 242-4243

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/stem-cell-therapy-is-one-step-closer-to-becoming-law-in-texas-300461859.html

SOURCE StemGenex

http://www.stemgenex.com

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Stem Cell Therapy is One Step Closer to Becoming Law in Texas - PR Newswire (press release)

Mouse study looks at safety of stem cell therapy for early ... Science Daily Now that we know that egg-making stem cells exist in adults and that these cells can be transplanted into mice with premature ovarian failure to produce ... and more »

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Mouse study looks at safety of stem cell therapy for early ... - Science Daily

NEW ORLEANS, LADespite new data showing that stem cell therapy has the potential to improve exercise time and reduce mortality in patients with refractory angina, researchers said at the Society for Cardiovascular Angiography and Interventions (SCAI) 2017 Scientific Sessions last week that the option is all but dead due to withdrawal of financial support, resulting in patients being denied access to a promising treatment.

Presenting a summation of all the data that have been collected over the last decade on the use of autologous CD34+ cells to treat patients with class III or IV angina despite optimal medical therapy, Thomas Povsic, MD, PhD (Duke Clinical Research Institute, Chapel Hill, NC), said this group of patients is in dire need of new treatment options, and maintained that it is imperative to explore methods to bring this therapy to patients.

He and colleagues conducted a meta-analysis from the only three trials of CD34+ therapy in refractory angina patients: a phase I study (n = 24); ACT-34 CMI and its 24-month extension study (n = 168); and the RENEW study (n = 112). All three were randomized, double-blind, placebo-controlled trials. However, RENEW was terminated early by the sponsor due to financial reasons.

Taken together, the trials showed that among the 187 patients who received the therapy, total exercise time improved by 90.5 seconds at 12 months compared with an improvement of just 39.5 seconds in those who received a placebo.

Additionally, patients who received CD34+ treatment had more than a fourfold lower rate of mortality by 24 months (2.6% vs 11.8%; P = 0.003) and fewer instances of MACE (29.8% vs 40.0%; P = 0.08).

A Cloudy Future

Povsic said the CD34+ trials are extremely expensive to run, resulting in the only sponsor, Baxter Healthcare, divesting itself of all further research in this area.

I personally believe that this therapy has more data associated with it for efficacy and safety than any other cell therapy thats been investigated in the cardiovascular disease space, he observed. The passage of the 21st Century Cures Act may hold some hope for the future, Povsic added, since it allows for a therapy that fulfills a specific medical need to undergo expedited approval.

Its challenging because this patient population has no options, Povsics co-author Timothy Henry, MD (Cedars-Sinai Heart Institute, Los Angeles, CA), said in a press briefing prior to the presentation. This is by far the strongest data for any therapy for refractory angina. Its also the . . . strongest data for cell therapy, and its a shame that its not available to patients.

Henry added that hes hopeful the data from the meta-analysis may be well received by the US Food and Drug Administration.

Povsic noted that although other companies have expressed interest in the therapy, its future is cloudy. Referencing the termination of RENEW for financial reasons, he added that it shows the ramifications that early cessation of a clinical trial can have, because its truly a disservice to the patients that were enrolled in the trial, the investigators that invested time, and the fact that this therapy . . . seemed so close to the finish line, but [now] the path forward is unclear.

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Access Denied: Stem Cell Therapy Shows Some Promise in Refractory Angina, but Patients Can't Get It - TCTMD

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The affiliates of the Stem Cell International are devoted to advancing access and quality care in the area of adult stem cell regenerative medicine in order to help people suffering from a variety of inflammatory and degenerative conditions.

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**SCI (Stem Cell International) does not claim to cure any disease or condition stated above. Note: We as a company have invested in state of the art equipment designed to uitilize a combination of growth factors (i.e. adult stem/Stromal cells), allowing us to harness your body's NATURAL restorative properties. We have had training from world renowned specialists on reintroducing your own stem/Stromal cells to activate your body's amazing ability to regenerate, promoting wellness through Regenerative Medicine.

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May 18, 2017

Now that we know that egg-making stem cells exist in adult rodents and humans and that these cells can be transplanted into mice with premature ovarian failure to produce offspring, the next question is to assess whether the offspring from the egg-making stem cells of a single adult mouse are biologically normal compared to natural births. On May 18 in the journal Molecular Therapy, researchers in China show that female mice with early menopause that receive egg-making stem cells from another mouse are capable of producing healthy pups 2 months later with no observable genetic malfunctions.

"One of our aims is to cure the disease of premature ovarian failure using female germline stem cells," says senior author Ji Wu, a reproductive biologist at Shanghai Jiao Tong University. "Before this treatment can be applied to humans, we need to know the mechanism of female germline stem cell development and safety after transplantation of single mouse female germline stem cells."

Premature ovarian failure, also called early menopause, is the loss of normal ovarian function, and thereby the release of eggs, before the age of 40. The condition is rare, affecting 200,000 women in the United States per year, and is incurable, although it can be treated with hormone supplements. Multiple groups are now looking at whether stimulating tissue regeneration or using stem cell transplants could help.

In the Molecular Therapy study, Wu and her colleagues isolated and characterized female germline stem cells from a single transgenic mouse with cells that show green fluorescence when activated by a blue laser. This allowed the researchers to observe and analyze the development of the transplanted stem cells, which were introduced to the ovaries of other mice using a fine glass needle.

Wu and colleagues found that the transplanted egg-producing stem cells exhibited a homing ability and began to differentiate into early-stage oocytes when they reached the edge of the ovary. The oocytes spent a few weeks maturing and yielded offspring within 2 months. The researchers then demonstrated that the developmental mechanisms of eggs derived from transplanted germline stem cells were similar to that of normal eggs.

"The results are exciting because it's not easy to get offspring from female germline stem cells derived from a single mouse," Wu says.

Wu's lab is also working to establish female egg-producing stem cell lines from scarce ovarian tissues derived from follicular aspiratesthe leftover cells gathered when a clinician searches a patient for oocytesthat are produced and discarded in in vitro fertilization centers worldwide. These aspirates can yield stem cells that differentiate into eggs in the lab, with the potential to be transplanted. The study not only provides a new approach to obtain human female germline stem cells for medical treatment, but also opens several avenues to investigate human oogenesis in vitro.

Explore further: Making sperm from stem cells in a dish

More information: Molecular Therapy, Wu et al.: "Tracing and characterizing the development of transplanted female germline stem cells in vivo" http://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(17)30180-6 , DOI: 10.1016/j.ymthe.2017.04.019

Journal reference: Molecular Therapy

Provided by: Cell Press

In a turnabout, a biochemical self-destruct trigger found in many other types of cells appears to guard the lives of brain cells during an infection with West Nile virus.

Researchers have discovered that protection from the most severe form of malaria is linked with natural variation in human red blood cell genes. A study from the Wellcome Trust Sanger Institute, the Wellcome Trust Centre ...

A protein called ZFP568 regulates an important fetal growth hormone called insulin-like growth factor 2 (Igf2), according to a mouse study led by researchers at the National Institutes of Health. The study is one of the first ...

Now that we know that egg-making stem cells exist in adult rodents and humans and that these cells can be transplanted into mice with premature ovarian failure to produce offspring, the next question is to assess whether ...

It's a fat-burning secret anyone interested in bone health should know. For the first time, UNC School of Medicine researchers show that exercising burns the fat found within bone marrow and offers evidence that this process ...

A Cedars-Sinai-led team of investigators has successfully repaired severe limb fractures in laboratory animals with an innovative technique that cues bone to regrow its own tissue. If found to be safe and effective in humans, ...

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Mouse study looks at safety of stem cell therapy for early menopause - Medical Xpress

During iwCLL, on 15th May 2017, the Additional Therapies for the Relapsed/Refractory CLL Patient session took place and was co-chaired by Michael Keating (MD Anderson Cancer Center) and Jacqueline Barrientos (The Feinstein Institute for Medical Research).

Anti-CD19 CAR-T Cell Therapy With Defined T-Cell Subsets for Ibrutinib-Refractory CLL was a presentation given during this session by David G. Maloney, MD, PhD, from the Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Maloney began by explaining that CAR-T cells produced from distinct T-cell subsets differ in potency. NSG mice bearing Raji tumors (0.5x106 tumor cell inoculation; day 0) were treated with human CAR-T cells manufactured from distinct T-cell subsets (on day 7). CAR-T cells produced from CD8+ TCM cells were highly potent (Sommermeyer et al. 2015).

Engineering selected T-cell subsets could enhance potency and allow delivery of the same cell product in all patients, potentially providing more uniform data on dose response and toxicity.

Pre-clinical studies have established that a defined composition of CD8+ TCM derived and CD4+ derived CAR T-cells provides optimal potency.

The talk then focused on the outline of the phase I/II study of JCAR014 in adult B-cell ALL, NHL, and CLL patients (NCT01865617).

As of 9/1/16, 136 patients had been treated: ALL = 48, NHL = 64, and CLL = 24.

Dose Level

Cells/kg

1

2x105 EGFRt+

2

2x106 EGFRt+

3

2x107 EGFRt+

Lymphodepletion and JCAR014 immunotherapy in high-risk CLL patients:

Treatment

N=24

Lymphodepleting chemotherapy

Cyclophosphamide/fludarabine (Cy/Flu)

21 (87%)

Non-Cy/Flu

3 (13%)

CAR-T cell manufacturing

CD8+ central memory and CD4+

7 (29%)

CD8+ all subsets and CD4+

17 (71%)

CD19 CAR-T cell dose level

DL1 (2x105 EGFRt+ cells/kg)

4 (17%)

DL2 (2x106 EGFRt+ cells/kg)

19 (79%)

DL3 (2x107 EGFRt+ cells/kg)

1 (4%)

Cycles

Single cycle

18 (75%)

Outpatient lymphodepletion and CAR-T cells

18 (75%)

Second cycle for residual disease or relapse

6 (25%)

Maloney then asked can IGH sequencing of the marrow at 4 weeks after JCAR014 identify patients with better outcomes?

Additionally, higher JCAR014 counts in the blood after infusion were associated with better bone marrow response in high-risk CLL. Patients with a higher peak CD3+/EGFRt+ CAR-T cell count in the blood had a reduced hazard of progression or death (HR, 0.56; 95% CI, 0.340.93; P = 0.025).

Maloney concluded that in high-risk CLL patients CD19 CAR-T cells of defined composition (JCAR014) can be administered with an acceptable early toxicity profile. JCAR014 and Cy/Flu lymphodepletion shows a high-level or anti-tumor activity as measured by:

Deep marrow clearance by IGHseq after JCAR014 provides early signs of durable responses with 100% PFS and OS.

Lastly, Maloney presented evidence that ROR1 presents as a novel target for CAR-T cell therapy for CLL, MCL, and solid tumors as it is highly expressed on the surface of malignant B-cells:

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Anti-CD19 CAR-T cell therapy with defined T-cell subsets for ibrutinib-refractory CLL presentation at iwCLL 2017 - Lymphoma Hub