Module 9 2021

19/03/2021

CAR-T Cell Therapy

Chimeric antigen receptor-T (CAR-T) cell therapy ● A new class of cancer therapy called immunotherapy, that activates a patient's own immune system to target cancer cells – Pronounced activity in certain cancers – 2 recent approvals for CAR-T therapy to treat acute lymphoblastic leukemia and large B-cell lymphoma (Kymriah and Yescarta) – Mechanism of action not completely understood

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The Organisation for Professionals in Regulatory Affairs

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Kymriah: Non-clinical Studies

As no relevant animal model available, standard single and repeat dose toxicity studies could not be performed Non-clinical studies conducted, include: ● in vitro and in vivo primary pharmacodynamic studies ● One non-clinical bio-distribution study in NOG mice (severely immunodeficient mouse model) ● Genotoxicity studies utilising DNA samples from 12 treated subjects and 2 healthy volunteers ● Other toxicity studies included: – investigations on the excipients – an in vivo safety assessment of tisegenlecluecel in mice – 3 in vitro expansion profile studies of CART-19 transduced T cells – tissue cross-reactivity using a murine CD19 chimeric antigen receptor – immunohistochemistry in situ hybridization and RTPCR analysis on human and cynomolgus monkey CNS tissue

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The Organisation for Professionals in Regulatory Affairs

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