Dr. Sotomayor on Differences Between FDA-Approved CAR T-Cell Therapies

Eduardo Sotomayor, MD
Published: Friday, Sep 20, 2019



Eduardo Sotomayor, MD, professor of medicine, Department of Hematology and Oncology, and director, GW Cancer Center, discusses differences between FDA-approved CAR T-cell therapies.

There are 2 FDA-approved CD19-directed CAR T-cell therapies: axicabtagene ciloleucel (axi-cel; Yescarta) and tisagenlecleucel (Kymriah). Both products are approved for the treatment of relapsed/refractory non-Hodgkin lymphoma, but tisagenlecleucel is also approved for pediatric patients with acute lymphoblastic leukemia. Although both products target CD19, they have different co-stimulatory domains, explains Sotomayor. CD28 is the costimulatory domain for axi-cel, whereas 4-1BB is the costimulatory domain for tisagenlecleucel. CAR T cells that rely on CD28 are more potent but have a shorter half-life, adds Sotomayor. Conversely, 4-1BB is less potent but has greater CAR T-cell persistence.

Now, researchers are investigating ways to extend the persistence of CD28 costimulatory products without decreasing efficacy. Research is also being dedicated to minimizing the toxicities associated with these products by modulating inflammatory cytokines, says Sotomayor. This approach may reduce the incidence of cytokine release syndrome and neurotoxicity.
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Eduardo Sotomayor, MD, professor of medicine, Department of Hematology and Oncology, and director, GW Cancer Center, discusses differences between FDA-approved CAR T-cell therapies.

There are 2 FDA-approved CD19-directed CAR T-cell therapies: axicabtagene ciloleucel (axi-cel; Yescarta) and tisagenlecleucel (Kymriah). Both products are approved for the treatment of relapsed/refractory non-Hodgkin lymphoma, but tisagenlecleucel is also approved for pediatric patients with acute lymphoblastic leukemia. Although both products target CD19, they have different co-stimulatory domains, explains Sotomayor. CD28 is the costimulatory domain for axi-cel, whereas 4-1BB is the costimulatory domain for tisagenlecleucel. CAR T cells that rely on CD28 are more potent but have a shorter half-life, adds Sotomayor. Conversely, 4-1BB is less potent but has greater CAR T-cell persistence.

Now, researchers are investigating ways to extend the persistence of CD28 costimulatory products without decreasing efficacy. Research is also being dedicated to minimizing the toxicities associated with these products by modulating inflammatory cytokines, says Sotomayor. This approach may reduce the incidence of cytokine release syndrome and neurotoxicity.

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