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Cell Therapy 360

What is CAR T-cell therapy?

CAR T-cell therapy is a form of immunotherapy that uses specially altered T cells a part of the immune system to fight cancer. A sample of a patient's T cells are collected from the blood, then modified to produce special structures called chimeric antigen receptors (CARs) on their surface. When these CAR T cells are reinfused into the patient, the new receptors enable them to latch onto a specific antigen on the patient's tumor cells and kill them.

Read more about how CAR T-cell therapy works

Currently, CAR T-cell therapy is FDA approved as standard of care for:

There are also many clinical trials of CAR T-cell therapy for other types of blood cancer and solid tumors.

For adult patients, call 877-801-CART (2278).For pediatric ALL patients, call 617-632-5064 or email gene.therapy@childrens.harvard.edu.

Read more about whether CAR T-cell therapy is right for you

Because this is a highly specialized, highly personalized treatment, CAR T-cell therapy is available at a limited number of cancer centers with specialized expertise in cellular therapies. Both Dana-Farber Brigham Cancer Center and Dana-Farber Boston Children's Cancer and Blood Disorder Center offer the FDA-approved CAR T-cell therapy as well as CAR T clinical trials.

Coverage is reviewed on a case-by-case basis, as is typical for new therapies. We work with patients and insurers to seek health insurance coverage for clinically-eligible patients.

Although most patients do not experience the common side effects associated with chemotherapy such as hair loss, nausea, and vomiting, there are risks of significant side effects with CAR T-cell therapy. Patients are monitored closely to manage reactions to this therapy. The complications are generally temporary and resolve with treatment. Our care team is specially trained to identify and manage these side effects.

Possible side effects from CAR T-cell therapy include:

Read more about potential side effects of CAR T-cell therapy

The treatment process involves:

Recovery can take time as your immune system recovers. The acute recovery period is typically for 30 days after the CAR T-cell infusion. During this time, patients must remain within two hours of Dana-Farber Brigham Cancer Center, and must have a caregiver with them at all times to monitor for signs of fever, infection, and neurologic difficulties. Most patients feel tired and don't have much appetite during this period.

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Frequently Asked Questions About CAR T-Cell Therapy - Dana ...

Construction of the new POCare Center, to be known as the Maryland Center for Cell Therapy Manufacturing, has been funded in part by a $5m grant from the State of Maryland; and the 7,000-square-foot facility has been designed to meet US Food and Drug Administration standards.

The facility will provide Johns Hopkins clinicians and researchers with a more streamlined path to treat patients and take promising and novel treatments from the lab to patient trials.The model provides local capacity for processing of clinical therapeutics at the point of care, rather than having to outsource clinical trial cell and gene therapy manufacturing to third parties.

The establishment of the new POCare Center will also enable rapid scale up of additional processing capacity through connecting/servicing Orgenesis Mobile Processing Units and Labs (OMPULs): which can shorten the implementation time of new capacity from 18-24 months to 3-6 months.

Construction of the center is expected to start in Q2 2022 and be operational in Q2 of 2023.Orgenesis will base 30 employees on the site when it is completed.

Founded in 2012, Orgenesis is a Germantown, Maryland based biotech: focused on developing cell and gene therapies in an affordable and accessible format at the point of care. The Orgenesis POCare Platform consists of three components: a pipeline of licensed POCare Therapeutics that are processed and produced in closed, automated POCare Technology systems across a collaborative POCare Network.

The company identifies promising new therapies, using its platform to provide a harmonized pathway for therapies to reach and treat large numbers of patients thanks to efficient, scalable and decentralized production.

Orgenesis continues to develop and extend key partnerships within its international POCare Network. These international partnerships are now experiencing significant investment and construction across the globe to build on the achievements within the Network, as illustrated by our expanded collaboration with Johns Hopkins, said Vered Caplan, CEO, Orgenesis.

We are honored to work with Johns Hopkins, America's first research university and home to nine world-class academic divisions working together in one university. The POC Center at Johns Hopkins will help propel the development of therapies targeting a range of conditions that directly affect the lives of millions of patients.

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Orgenesis and Johns Hopkins University create Maryland Center for Cell Therapy Manufacturing - BioPharma-Reporter.com

"However, there are limited automated solutions in this area, much less specific to formulation, fill, and finish, that genuinely address the market needs,"Kathie Schneider, director, global commercial lead, andDalip Sethi, director, scientific affairs, Terumo BCT, told us.

Terumo Blood and Cell Technologies (BCT), a US-based medical technology firm and subsidiary of Tokyo-based Terumo Corporation, has been focusing on innovation in downstream technologies to automate the final steps involved in autologous cell therapy manufacturing.

Final formulation is considered one of the most critical steps in the autologous cell therapy manufacturing process but manydevelopers are still performing this process manually, they said.

"To get drug products to scale in manufacturing, automation is required. Solutions must maintain the viability of the product as much as possible so that the cells are able to proliferate inside the body. This is further complicated with autologous products; one product is one batch. Therefore, finding automated solutions can be a challenge due to the smaller batch sizes.

"Uniquely maintaining drug products at ultralow temperatures, that can maintain the products viability from the fill/finish stage through infusion is also a challenge. The complex final formulation steps involve the addition of pre-cooled cryoprotectants and maintaining the cell product at low temperature for a short duration before freezing, which can limit the batch size of the drug product."

In the addition of pre-cooled cryoprotectants, cells are mixed with dimethyl sulfoxide (DMSO) and that process needs to be managed very carefully so as not to harm the cells, via slow addition with chill plates, said the Terumo team.

Managing the DMSO addition, accurately aliquoting into specific bags, sealing the bag, and maintaining batch records leave opportunities for errors.With manual processes, we have found customers lose cell viability, experience operator-related product variability, experience contamination due to open events, and errors in data logging.

Terumos automated Finia system, made available to the market in 2020, addresses this final step.

The Finia system automatically adjusts product temperature, as per users protocol, with the mixing and cooling assembly for cells, buffer, and DMSO. The system accurately aliquots the desired volume across three product bags plus a QC bag. Finally, the system removes air, seals the product bags for downstream, cryopreservation, and logs the steps for export into batch records, thus making this process much more scalable as manufacturers manage increased patient volume.

Terumo found that in this process, the product maintained >90% post-thaw cell viability. Finia hands-on time is typically 6.4 minutes versus 56.7 minutes when performed manually.

Excerpt from:
De-risking cell therapy manufacturing with downstream technology innovation - BioPharma-Reporter.com

Cell and gene therapy developers globally raised an all-time annual record in 2021. However, European firms missed out on the funding growth.

Companies around the world developing cell and gene therapies raised 20.1B ($23.1B) over 2021, said the advanced therapy advocacy organization the Alliance for Regenerative Medicine (ARM) in a briefing this week. This bumper catch beat 2020s total of 17.3B ($19.9B) by 16%.

The growth from 2020 to 2021 was primarily driven by companies in the US. With a fresh 15.7B ($18B) in the bank, US-based companies saw an impressive 53% jump in investments compared to 2020. In contrast, their European counterparts raised 2.9B ($3.3B), 8% less funding than in 2020.

Both European and US gene and cell therapy players had seen record funding growth in 2020 compared to 2019, said Stephen Majors, ARMs Director of Public Affairs. However, its too early to establish why European and Asian companies havent matched the rapid cash growth seen in the US over 2021.

Its something well watch closely over the next year to determine what the causes may be and whether they are region-specific, said Majors.

Nonetheless, the funding numbers need to be interpreted in the correct context, said Antoine Papiernik, Chairman and Managing Partner of the venture capital (VC) firm Sofinnova Partners. European contributions to the field of cell and gene therapy remain immense.

Its not about how much you raise in one year; its about the level of expertise, competencies, and technologies, said Papiernik. These are the fundamentals for long-term excellence and growth, which we strongly believe in.

If there is one area where Europe is, without a doubt, on par with the US, its in new modalities, which include gene and cell therapies.

Of the various funding sources going to cell and gene therapies, VC funding increased the most in 2021, with a huge 73% jump to 8.5B ($9.8B). This trend mirrored the deluge in life sciences VC funding in the last year.

Simultaneously, gene and cell therapy companies were hit by struggling stock markets affecting the rest of the biotech sector. This mismatch is creating a bulge in funding for VC firms and potentially limiting exit options.

Inflation concerns made it particularly difficult for smaller, early-stage companies that are not yet profitable, said Majors. If inflation concerns subside in 2022, and with positive data readouts, we could see stronger performance for biotech public equities.

When the total is broken down by the types of technology getting funded, cell therapies in immuno-oncology such as CAR-T cell therapies saw the biggest funding increase: a jump of 26% since 2020. This was followed by gene therapy firms with 14% more incoming cash, and tissue engineering players, whose investments went up by 10%.

Cell therapy companies outside of immuno-oncology experienced a tighter year for financing in 2021 than in 2020, taking in 15% less funding at 1.7B ($2B). However, Majors told me that funding in this field has regularly fluctuated in the last several years.

The decrease over 2021 is not an outlier in comparison to historical trends, Majors noted. Due to the smaller size of this technology segment, just one or two financing deals can have a large impact on total financing on an annual basis.

Another important trend in the ARMs report was the rising importance of gene-editing technology. Of the total gene therapy financing, 45% was raised by companies developing gene-editing technology, up from 38% in 2018.

Investor interest in gene editing has been buoyed by clinical successes from frontrunner gene therapy players in the last year. One example from June 2021 was the promising performance of an in vivo CRISPR treatment developed by Intellia Therapeutics and Regeneron in patients with the rare disease transthyretin amyloidosis.

Gene-editing firms CRISPR Therapeutics and Vertex Pharmaceuticals are causing excitement with progress in tackling the blood disorder sickle cell disease. They are gunning to file for approval of their CRISPR gene-edited therapy for this condition in late 2022.

Investors have taken note of these early successes and see this approachs potential to treat a wide range of diseases, said Majors. Also, as this technology continues to progress, the number of companies with at least one clinical or preclinical asset in gene editing continues to rise.

Another outcome to look forward to for gene and cell therapy in 2022 is a potential record number of drug approvals. A bunch of gene therapy hopefuls including GenSight, uniQure, and BioMarin are poised to bring their candidates to the regulatory finish line in the US and Europe.

The EMA is slated to make decisions on therapies targeting aromatic l-amino acid decarboxylase deficiency, Leber hereditary optic neuropathy, and two types of hemophilia, said Majors. By the end of 2022, the number of EMA-approved gene therapies for rare diseases may have doubled from a year earlier.

However, some of the major hurdles for the field will likely be the delivery of gene and cell therapies to their target in the body as well as deciding the right dosage. The manufacture of these complex therapies is also a big bottleneck that many startups aim to tackle.

Additionally, the withdrawal of bluebird bios gene therapy from Germany in May 2021 over pricing disagreements demonstrates that regulatory approval is just the beginning for developers of gene and cell therapies. Their pricing strategy will need to walk the tightrope of making a profit while avoiding clashes with healthcare systems.

In any case, European companies will continue to play a strong role in the evolution of the cell and gene therapy sphere.

Lets not forget that the first gene therapy to be brought to the market was European, said Papiernik, referring to the gene therapy Strimvelis, which was sold by GlaxoSmithKline to Orchard Therapeutics in 2018.

Europe continues to excel in the development of gene and cell therapies and never has there been more opportunities for investment.

Cover image via Elena Resko. Inline images via the Alliance for Regenerative Medicine

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Europe Trailed US in Record Gene and Cell Therapy Funding in 2021 - Labiotech.eu

To repeat the success of CAR-T therapies in blood cancers,a key direction for solid tumor research focuses on enabling the engineered immune cells to better target those tumors. Now, a group of scientists in Italy has proposed a method to do just that.

Sugar-based structures called N-glycans, which are expressed on the surface of pancreatic tumor cells, could protect the cancer from CAR-T cells, scientists at the IRCCS San Raffaele Scientific Institute have found. Disruption of the coating with a sugar analog dubbed 2DG enhanced CAR-T killing in different mouse models of pancreatic tumors and showed promising efficacy against other cancers in lab dishes.

The findings, published in Science Translational Medicine, could pave the way to designing improved CAR-T cell therapy strategies against pancreatic cancer and other solid tumors, the researchers said.

Glycosylation, the process by which sugar-based molecules attach to and modify a protein, plays an important role in cellular processes. Cancer cells display abnormal glycosylation, with the expression of a more diverse glycan coat compared with healthy cells. Among them, an increase in N-glycans is among the most frequent alterations found in cancer.

RELATED:Turning CAR-T tech against solid tumors by targeting protein fragments in cancer cells

For their study, the San Raffaele researchers hampered branched N-glycan in pancreatic tumor cells by crippling the MGAT5 gene, which encodes for an enzyme key to the synthesis of the sugar-based coat. They treated the cancer cells with CAR-T cells directed at CD44v6, a heavily glycosylated protein. The CAR-T cells showed markedly enhanced antitumor activity with increased cancer-killing and the production of the proimmune cytokines interferon-gamma and TNF-alpha.

By digging deeper into the mechanism behind the improved efficacy, the researchers found that N-glycans interfered with the formation of immunological synapses. CARs rely on such synapses with tumor cells to activate the T cells and exert their functions.

The team then tried blocking N-glycan with the glucose analog 2DG. In two xenograft mouse models of pancreatic cancer, a combination of 2DG and the CAR-T cells showed the best tumor control, significantly prolonging the survival of mice compared with either single treatment alone, the team reported.

Whats more, in mice that also received 2DG, T cells that entered the tumors showed a reduced exhaustion profile with lower expression of several immune inhibitory markers such as TIM-3 and PD-1. Exhaustion of T cells, which could be caused by sustained antigen stimulation and the expression of inhibitory receptors, is a major obstacle to CAR-T cell efficacy against solid tumors.

These findings suggest that combination with 2DG not only improves tumor clearance but might also enable CAR-T cells to evade immune checkpoint inhibition, the researchers wrote in the study.

Beyond pancreatic cancer, the addition of 2DG also helped increase the killing of other highly glycosylated tumors that CD44v6 CAR-T alone failed to tackle, including in mice with bladder cancer and ovarian cancer.

RELATED:Biopharma charts progress in translating CAR-T cell therapies to solid cancers

CAR-T therapies such as Gilead Sciences Yescarta have demonstrated impressive results in blood cancers, and scientists are in hot pursuit of effective solutions to overcome the many barriers that stop the immunotherapy from working in solid tumors.

To tackle the problem ofthere being a lack of appropriate tumor-specific antigens thata CAR can target,a team at the University of Pennsylvania's Childrens Hospital of Philadelphiadesigned peptide-centric CAR-T cells to hunt down fragments of cancer-related proteins that are revealed to immune cells through antigen-presenting MHC proteins.

Canadian biotech Oncolytics Biotech is working on an oncolytic virus called pelareorep to alter the hostile tumor microenvironment that could suppress T-cell activity. Working with Mayo Clinic, the company previously showed CAR-T cells armed with the virus enhanced antitumor activity in mice with solid tumors.

The San Raffaele team now believes breaking down the sugar barrier around tumor cells represents a promising strategy to overcome solid tumors'resistance to CAR-T therapy by improving CAR-T cell activation and alleviating CAR-T cell exhaustion.

Our findings point to the therapeutic potential of combining CAR-T cells with 2DG to counteract multiple layers of tumor resistance including the inadequate tumor engagement and the damaging effects of inhibitory pathways, the researchers said in the study.

More here:
Stop sugarcoating cancer cells to empower CAR-T therapy in solid tumors - FierceBiotech

CAR-T cell therapy has been a boon for treating blood cancers. Since the technology was first brought to the clinic, CAR-T has offered patients months or years of life after they had exhausted all other treatment options and would have died within weeks.

Its been incredible, said Marcela Maus, an immunologist and cell therapist at Mass General Cancer Center. Weve seen patients who had multiple lines of therapies and progressed after all of those, [then] get CAR-T and go into long-term remission.

But CAR-T does have hefty limitations, and scientists like Maus are researching ways to overcome some of its major shortcomings. These issues have prevented CAR-T from being used safely and effectively outside of leukemia and myeloma, and even patients who have responded spectacularly to CAR-T usually see their cancers return. The therapies are also still incredibly costly and carry risks, including a reaction known as a cytokine storm that can be life-threatening.

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Potential solutions to these problems are still in the early stages, but scientists are beginning to get a vision of what the future of CAR-T cell therapy might look like. It could involve synthetic biology to engineer a more advanced cell, or engineering other parts of the T cell to make it work better in the challenging environment around a tumor.

The field is growing tremendously, Maus said. Different people are working on different issues then, ideally, the data kind of decides whats going to be the next big thing.

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Heres a look at what experts see as some of the most promising approaches.

Current CAR-T cells use their CAR, or chimeric antigen receptor, to identify and kill cancer cells. These are synthetic proteins that bind to a specific target, like a protein on a cell surface membrane, and then activate the T cell to kill any cell carrying this target.

Armed with a CAR, T cells become pros at killing cancer cells that have their target, but theyll also kill normal cells that happen to carry the protein, too. Once a CAR-T cell is in the body, there isnt much a clinician can do to rein it in if it starts causing a lot of toxicity.

Once we let the CAR out, theyre like teenage kids, Maus said. You can maybe watch, but you cant really control them. So, theres some desire to be able to turn them on or off at will.

So, researchers are also trying to create CAR-T cells that they can manually activate or deactivate. As a group, these are known as controllable CARs, and most work by engineering an additional genetic circuit in the CAR-T cell. In theory, clinicians should be able to activate a switch on the genetic circuit that induces the CAR-T cell to activate their CAR and express it on the T cells surface membrane, thereby activating the receptor. Then, after a while, the T cell will disarm.

The goal is really getting our hands back on the steering wheel for a bit, Maus said.

There are several ways that synthetic biologists are doing this. In one example, researchers engineered a CAR with a protein switch that activates the receptor in the presence of blue light. In another example, researchers added a gene to CAR-T cells that force it to create its CAR and express it on the cell surface, thereby activating it, only in the presence of ultrasound radiation.

That way, it can be focused into a specific location, said Peter Yingxiao Wang, a synthetic biologist at University of California, San Diego, who works on controllable CARs. When the light or ultrasound is on the tumor locally, they can activate the CAR gene to trigger killing. Anywhere else, the CAR T-cells will be benign.

The idea is that the clinician can focus the light or ultrasound onto the tumor to get CAR-T cells to begin killing there. Once that signal is turned off, the CARs should disarm or slowly degrade and deactivate the CAR-T cells killing function. This way, even if the CAR does kill healthy tissue, the damage will theoretically be limited to the area around the tumor.

But this is an infant field right now, Wang added. A lot of these studies are just proof of concepts to show that theyre technically achievable. If you want to move to clinical trials, all of the components must be optimized.

Scientists also must show that theyre truly safe in humans, and that keeping the damage to a smaller surface area will be enough to outweigh the risks in treating tumors located near vital organs like the heart.

Other researchers are working on developing new CARs that can function like a biomolecular computer, able to make simple logical decisions to target cancer cells. Conventional CARs can cause dangerous toxicity because they only use one protein to identify cancer cells, and it may be impossible to discover the perfect target that exists only on cancer cells and not at all on healthy cells.

You can never uniquely define cancer or any other healthy tissue just by one marker, explained Wilson Wong, a synthetic biologist at Boston University. It just doesnt work. Its like trying to find a person and saying, he has black hair. Its like, oh, my God, youll never find him.

But it might be possible to distinguish cancer cells from healthy ones by looking at multiple proteins on a single cell. So, researchers like Wong have begun building more advanced CAR T-cells that use genetic circuits that only activate a CAR under more complex conditions, like the presence of several specific proteins that arent often seen in combination on healthy cells.

In this sense, the CAR is making a logical decision like basic Boolean computing, and synthetic biologists call this technique logic-gating.

Theres a lot of cool genetic circuits you can build, said Yvonne Chen, a synthetic biologist at UCLA. One can think of conditional systems to obliterate cancer cells. One can build OR-gates, AND-gates, and NOT-gates, and layer them on top of one another.

Although, Chen added, a drawback of logic-gating is that by increasing the complexity of the system, you might also be increasing the chance something goes wrong. Its important not to overcomplicate the design. Sophisticated circuits are exciting, but sometimes the solution itself causes problems. For example, for an AND-gate, you also make it easier for the tumor to escape. If the tumor loses either target A or B, it escapes from therapy, she said.

Another issue with conventional CAR-T therapy is that after a while, T cells can simply stop working. Solid tumors, like lung or pancreatic cancer, often have strategies to defend themselves from immune system attacks, including those from CAR-T cells. That makes it harder for CAR-T cells to treat solid tumors and can provide an opening for the tumor to return or progress.

So, researchers like Chen are working on armoring the CAR T-cell against the hostile signals in the microenvironment around a solid tumor. One of these signals is called TGF-beta, a protein which can help shut down T cell activity and help cancer cells avoid death and detection from the immune system. Chen was able to create a CAR cell that is not only resistant to TGF-beta, but can actually subvert the signal and become more deadly when it encounters TGF-beta.

Instead of being dysfunctional, they become activated, Chen said. That actually converts a tumor defense mechanism into a stimulatory signal for our T cells and tells them, youre in an environment where youre likely to encounter a tumor cell. Get ready.

Other scientists are working to keep CAR-T cells which can lose power over time functional for longer. Even with a good antigen, the T cells rapidly lose function, said Shivani Srivastava, an immunologist at the Fred Hutchinson Cancer Research Center who works on this problem. If you trigger a T cell or CAR over and over again, that causes the cell to become exhausted rather than turning into a memory cell or something else.

In one case, Stanford immunologist Crystal Mackall engineered a CAR-T cell that takes breaks before returning to work. She did this by creating a transient CAR that can be turned on or off. It can enhance [the T cells] function and limit how exhausted they are by giving them periodic rest, Srivastava said. Thats a really interesting strategy in principle.

But most of the tactics that scientists have tried so far in the realm of armored CAR-T cells havent worked in the long term, Srivastava said. You need a strategy that can help the CAR T-cells persist long enough to eradicate the cancer and prevent its return, which might be a lifelong project for the immune system.

Well have to find the right combination that will be durable, she said. Often we can find strategies that enhance function for only a short period of time.

Some future approaches might see T cells abandoned altogether. Scientists are slapping synthetic receptors on new or different cell types, such as natural killer cells. One company, called CoImmune, is putting CARs on a synthetic cell called a CIK cell, or cytokine-induced killer cell.

This is a novel cell type. They dont occur in nature, explained Charles Nicolette, the biotechs chief executive.

Theyre made by taking white blood cells and growing them while exposing them to certain immune molecules called cytokines. The advantage of creating new cell types is that biologists can combine certain useful traits from other immune cells, Nicolette said. For example, CIK cells could have the NK cells natural ability to distinguish normal cells from malignant ones and the CAR T-cells enhanced ability to kill.

One day, UCLAs Chen hopes to take this concept even further. To her, the ideal cancer-killing cell would not be derived from anything biological, but a completely artificial cell.

Instead of taking a cell from a patient, but rather build a completely defined, minimal cell that can do what we want and nothing else. It cannot evolve. Cannot mutate. Then, self-destruct when you dont want it there, she said. But, she added, creating synthetic cells like that would be unimaginably challenging, and it might not be possible to create a cell thats both persistent but also unchangeable.

Still, a scientist can dream.

Link:
STAT's guide to the next generation of CAR-T therapies - STAT

Lonza will work with Agilent to define the ideal Critical Quality Attributes (CQAs) for cell therapy manufacturing and help better control the in-process controls and analytics of its patient-scale Cocoon platform.

Lonzas Cocoon platform is a single system that can be used for a variety of different autologous cell therapy protocols, with each patient batch produced in a single disposable cassette customized to their specific process.

The automated point-of-care manufatcuring system was developed by Octane Biotech, and though Lonza has worked with the firm since 2015 to help develop the platform, it acquired a controlling stake in the company in October 2018, describing the tech at the time as a game changer in the autologous cell therapy space.

Image: c/o Lonza

Now Lonza is looking to optimize the platform by addressing the actual needs of the autologous cell therapy production space through a collaboration with analytics firm Agilent Technologies.

Agilent is a leader in the field of analytics, Nicholas Ostrout, senior director of Business Strategy & Implementation, Personalized Medicine, Lonza told BioProcess Insider. We found their portfolio of technologies compelling, based on their participation in important research work that supports key advancements in cell therapy.

We decided to leverage the existing innovative technologies of an established player in the market rather than reinvent these tools ourselves. By partnering with Agilent, we can bring these technologies to the market faster and within platforms that the field is familiar with.

The collaboration aims to develop and integrate current and new analytical technologies into patient-scale cell therapy manufacturing workflows with the Cocoon Platform, but also hopes to define the ideal Critical Quality Attributes (CQAs) required for cell therapies and build improved analysis packages to manufacture higher quality therapeutic products with greater consistency.

Generally speaking, the field is still in its infancy in its understanding of the CQAs required to manufacture a safe and efficacious product; there is a lack of clinical experience with cell and gene therapy (CGT) products, compared to other, more well-studied classes of pharmaceutical products, Ostrout said.

Therefore, the field is still developing a basis of understanding to define CQAs associated with a safe and efficacious product. The process is made even more complex by the fact that, unlike many other therapeutics, CGT products may persist in humans long-term, and are likely to evolve over time, thus necessitating a contextual understanding of product safety and efficacy within given indications and patient populations.

Since the addition of the platform, Lonza has publicized several deals with companies and establishments looking to use the Cocoon tech, but it has only been used in a clinical setting since late 2020. While the platform can currently control temperature, pH, and dissolved oxygen, Ostrout said Lonza plans to enhance integrated analysis technologies in the platform with a hope that it will be able to monitor more properties in real-time during the manufacturing process to assist in meeting required specifications.

There is value in generally establishing a deeper understanding of CQAs for cell therapies broadly in the field and implementing analysis technologies directly into the manufacturing platforms. As the field of cell therapy moves towards complete automation, we feel that there is an opportunity to begin integrating technologies directly into the manufacturing platform. This will assist in analyzing CQAs at relevant intervals during the process and understanding the key release criteria required to manufacture the ideal cell therapy for a given indication.

He added: The more functionality a closed system offers, the more compelling the automated manufacturing solution becomes. However, the quality of the therapy is obviously the most important aspect. As such, manufacturing platforms will have to become smarter to ensure the ideal product is manufactured for any given patient and indication. As therapies become more personalized, its critical that the manufacturing process can make adjustments in real-time.

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Lonza and Agilent to make Cocoon tech 'smarter' - BioProcess Insider - BioProcess Insider

Sony has introduced a new cell isolation system, CGX10, which sorts cells at high speed and high purity in a closed system. The CGX10s design enables sorting of cells in a manner that is entirely closed off from the outside environment, making it possible to analyze and isolate cells while maintaining a sterile state. This is especially important in fields such as cell-based immunotherapy, which has been gaining recognition as a treatment for cancer and autoimmune disorders. To produce the cell therapies necessary for this treatment, there is an increasing demand for isolating cells with high purity and high viability in a sterile manner.

It is also expected that this product could be utilized in research for developing cell-based products for fields such as cell therapy and regenerative medicine. It can also contribute to the development and production of cell therapies in compliance with quality and production management regulations.

By introducing CGX10, Sonys life science business will expand from research applications to the field of cell therapies development and manufacturing, further contributing to the advancement of cell therapy.

Cell-based immunotherapy treatment is gaining recognition as a treatment for serious diseases, such as cancer, says Taisuke Kawasaki, senior general manager, life science division, Sony. Our cell isolation system CGX10 integrates closed multi parameter cell sorting technology, making it possible to accelerate the development of cell therapies. With this product, we are able to move from contributing to life science research to supporting the production and development of cell therapies. We will continue to contribute to society for people's safety and security by leveraging Sonys technologies in the life sciences field.

Until now, the main treatments for cancer have been surgery, radiation therapy, and anticancer drugs. However, in recent years there have been rising expectations for cell-based immunotherapy to be the new, fourth pillar of cancer therapies, says James Graziadei, CEO of the Sony biotechnology business. In addition to a treatment for cancer, cell-based immunotherapy is also recognized as a new treatment for autoimmune disorders such as diabetes and rheumatism. Alongside medical development, demand will continue to grow for cell sorting under the highest levels of sterilization and purity. With the introduction of CGX10, well aggressively support cell therapies.

Sonys CGX10 features the ability to use up to 10 parameters to isolate a single cell, and the signal is based on excitation from four lasers (405nm / 488nm / 561nm / 638nm) to detect target cells of interest. At analysis speeds of about 15,000 cells per second, it also ensures a purity level of about 97% and higher.

By controlling fluidics, cell damage is minimized, allowing for a high viability of sorted cells. Thus, it can increase the efficiency of the downstream production processes, such as cell culture and expansion for producing cell-based therapies. Furthermore, as this instrument uses fully disposable, single-use plastic tubing/components, any risk of cross-contamination between samples is avoided.

Sony is expected to begin deliveries of the CGX10 cell isolation system in fall 2022.

Read the original here:
Sony System for Use in Production of Advanced Cell Therapy Products From: Sony - Healthcare Packaging

CASE SUMMARY:

A 73-yearold woman presented with shortness of breath, productive cough, chest pain, fatigue, anorexia, and recent 18-lb weight loss. She had a history of hypertension and was a 45 pack-a-year smoker. An examination showed she had dullness to percussion and decreased breath sounds.

A chest x-ray showed a left hilar mass and a 5.4 cm left upper lobe mass. A chest/abdomen/pelvis CT scan showed a hilar mass with bilateral mediastinal extension and was negative for distant metastatic disease. PET scan showed activity in the left upper lobe mass and supraclavicular nodal areas and liver lesions. An MRI showed one small asymptomatic brain lesion. An interventional radiology biopsy of the liver led to a diagnosis of small cell lung cancer (SCLC) and the patients ECOG performance score was 1.

DISCUSSION QUESTIONS:

MELISSA L. JOHNSON, MD: Is there any other workup that you would recommend before you start therapy?

MICHEL E. KUZUR, MD: I am wondering if molecular testing has any benefit here?

JOHNSON: Well, because this is a SCLC patient, I do think about molecular profiling, but I would not wait to get that result back to start therapy.

Because we know that this patients diagnosis is SCLC based on the liver, and that she had CT scans of the head and an MRI, and because we do not check PD-L1 status in SCLC, I would say our workup is complete, and I think we are ready to start therapy.

For what proportion of your patients with extensive-stage SCLC is treatment initiated in the inpatient setting?

JOHNSON: Most of the participants responded that the majority of your patients with SCLC are not started in the inpatient setting, which is good, so they should all be treated in a frontline trial.

DISCUSSION QUESTIONS:

JOHNSON: I often ask sponsors if they could let me give 1 cycle in the hospital because sometimes SCLC is a rapid diagnosis, especially with virulent symptoms, so you do not have time to wait to get them to the clinic to give chemotherapy. And so if there is 1 kind of chemotherapy I know how to give in the hospital, it is carboplatin/etoposide. Does anyone disagree?

JEFFREY FRIEDMAN, MD, PHD: I agree, but I think that for a lot of us in sort of peripheral clinics like where I practice, the issue is that it is somewhere in between needing inpatient chemotherapy and can I wait 4 weeks to get their tissue sampled for whatever it takes to get them on trial? Typically, even though I am not treating them in the hospital, I am not waiting weeks. They are getting started on treatment in a few days or else things are just going to completely go off the rails, and so I think that is the bigger hurdle when it comes to trial accrual. Even just the ancillary imaging that might be needed for a trial is just not doable.

GREGG C. SHEPARD, MD: The other issue is that probably 90% or more of patients I meet are treated for the first cycle in the hospital but then they are discharged and sent to Dr Friedman at a peripheral clinic, so he can give them a second cycle as an outpatient. So he may be choosing 90%. He treats people in the outpatient setting, but I am treating them for their first cycle usually inpatient at Ascension Saint Thomas Hospital.

JOHNSON: If you have a couple more days, and you are waiting for Dr Shepard to refer a patient to come see you, for example, or you have seen a patient at TriStar Southern Hills Hospital and you have asked them to come to clinic, what is your approach to selecting treatment? What is the algorithm that you go through when you are thinking about a new SCLC diagnosis?

JACK W. ERTER, MD: I mean, I think luckily in this disease, for better or for worse, it is not like there are 17 different options I am weighing the pros and cons of and saying, "Are they are going to be a candidate for up-front EGFR-targeted therapy or similar." I mean, this carboplatin/etoposide chemotherapy plus immunotherapy. That is what they are starting on, unless they have 4 brain metastases, in which case they need radiation treatment first.

NANCY W. PEACOCK, MD: The other thing I think is, a lot of these people that have SCLC that lands them in the hospital; they do not have a ton of psychosocial support. They delayed coming in until they got very sick because they did not have the wherewithal to get there. They do not have the support at home. They come in from the hinterlands and often the first conversation we have with them is, "This is really a very difficult diagnosis. I can give you treatment." Even if their ECOG performance status is 3, it might not be worth treating them. Everybody says, "Oh, SCLC responds," but SCLC with a poor performance status does not respond very well. I think as we are being held more and more accountable for this oncology as a cure model, trying to keep expenses down and people out of the hospital is a decision that is being made more and more, but the people I see mostly are under-insured and [not receiving enough care].

JOHNSON: Those are also absolutely relevant topics for this patient population especially. I would say that carboplatin/etoposide remains the mainstay of treatment and luckily that is cheap in the inpatient setting. Obviously, the hospitalization costs more, but it is immunotherapy that adds the true cost. But that is a good point. In terms of treatment options, how are you counseling your patients?

KUZUR: In support of what Dr Peacock mentioned, sometimes the hospitalist has already convinced the patient to go on hospice, and they consult hospice and they consult me. I sometimes have to find the option and try to convince them to try some therapy. Dr Peacock is right. Some of these people are so sick you are not able to justify that you are going to get some active results with treatment.

DISCUSSION QUESTION:

JOHNSON: Does anybody want to explain why you think carboplatin or why you recommend cisplatin for a SCLC patient?

RYAN M. CARR, MD: I almost always use carboplatin, but I guess one reason I would consider cisplatin is if they have some degree of myelosuppression from some other reason to begin with, and we are able to tolerate the cisplatin, then I guess I could consider that. But almost everybody gets carboplatin with me.

ERTER: Yes. I rarely would use cisplatin and I do not think there is a big advantage in extensive-stage SCLC. I might consider it in limited curative therapy.

JOHNSON: Agreed. I think that is what our entire practice would say, and so this patient [would get] concurrent atezolizumab [Tencentriq] with carboplatin/etoposide and that was based on the IMpower133 [NCT02763579] data.

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Approaches and Obstacles to Frontline Treatment for Small Cell Lung Cancer - Targeted Oncology