Module 9 2024

03/09/2024

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 leukaemia and large B-cell lymphoma (Kymriah and Yescarta) • Mechanism of action not completely understood

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

The Organisation for Professionals in Regulatory Affairs

Kymriah European Assessment Report 28 th June 2018

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