The next frontier of CAR-T cell therapies: Allogeneic workflows

The development of CAR-T cell therapies provides treatment options for some of the most vulnerable cancer patients, giving them a fighting chance to battle their diagnoses if they’re eligible. Researchers and organizations continue to work diligently to optimize the manufacturing process to develop safe and effective CAR-T cell therapies as efficiently as possible, with the hope that one day they can be manufactured at a lower cost and made available to any patient who could benefit from them.

Personalized therapies have shown incredible effectiveness, but there are inherent challenges in the traditional autologous workflow that relies on using a patient’s own T-cells. To develop the therapy, the isolated T-cells need to be grown ex vivo in a medium.

Unfortunately, cells taken from sick patients can be slow to grow due to the nature of the illness and the hostile environment the cells have lived in. From collection to reinjection, it can take on average 17 days to treat a patient with an autologous CAR-T cell therapy. This is an expensive and time-consuming process with little room for error when time is of the essence for patients who are desperate for treatment.

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One of the strategies that scientists are hopeful could make CAR-T cell therapies more accessible is a manufacturing workflow that uses cells from healthy donors. Unlike the traditional autologous CAR-T cell therapies that use a patient’s own T cells, allogeneic CAR-T cell therapies are manufactured using healthy donor cells, to be used to treat multiple patients as an “off-the-shelf” treatment. These healthy T cells are in much better condition to be reprogrammed, proliferated, and injected into the patient to fight the cancer. Even with healthy cells, the quality of the materials, such as the medium used, is critical.

“Cell culture media can play a direct role in maintaining the quality of the cells, but they are often overlooked. The quality of the cells is paramount, as it translates into enhanced potency or efficacy,” said Roderick O’Connor, research assistant professor at the Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania.

“Unfortunately, most media formulations were created years ago and contain supraphysiological levels of nutrients meant to support robust cell proliferation. However, this is not the best approach for cell-based therapies, as it can negatively affect the quality of the cells because advanced proliferation by this method can chew up telomeres, promote senescence and create oxidative stress.”

Gibco’s serum-free medium

In order to support the greater demands of healthy-donor allogeneic workflows, Thermo Fisher Scientific has developed Gibco CTS OpTmizer Pro Serum-Free Medium.

This medium maintains cellular youth in healthy donors, dramatically enhances healthy donor T-cell proliferation, delays effector differentiation of healthy donor T-cells and increases IFN-Ɣ production by healthy donor T-cells, making it uniquely positioned to support allogeneic workflows.

By increasing central memory cells early in the expansion protocol, this formulation yields larger cell numbers at harvest and in less time. In an 18-day expansion workflow, the average growth of the cells was approximately 20% higher for all donors by day 10, with an increase by day 17 of over 100% with no negative effect on viability.

“Our goal is to help cell therapy scientists develop a manufacturing workflow that will make CAR-T therapies accessible to as many patients as possible,” said Kate Torchilin, vice president and general manager of Bioproduction at Thermo Fisher Scientific. “By providing a medium specifically for allogeneic therapies, we are closer than ever to having an off-the-shelf treatment that will help in the fight against cancer.”

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