National Cancer Institute 5F30CA291106-03

Biologic and Functional Characterization of In Vivo CAR-T cells

This award supports research to develop in vivo engineered CAR-T cells using the PACK-IT system to improve efficacy, reduce manufacturing time and cost, and increase patient access to CAR-T cell therapy for B cell malignancies.

Description

Chimeric Antigen Receptor (CAR) T cell therapy has revolutionized treatment for B cell malignancies by targeting T cytotoxicity to the site of the tumor. Despite the success of CAR-T cells in B cell malignancies, more than half of patients receiving CAR-T cell treatment fail to achieve long-term disease control. Therapeutic failure can be attributed to many causes including the inverse relationship between CAR-T cell manufacturing duration and the resulting anti-tumor potency. Additionally, CAR-T cell manufacturing poses barriers to access such as cost and difficulty meeting supply demand. To engineer the next generation of CAR-T cells with enhanced anti-tumor efficacy and greater patient access, CD19.28z CAR-T cells will be generated in vivo using modified lentiviral particles engineered to express a T cell targeting antibody fragment, referred to as the PACK-IT system. The system will explore the hypothesis that in vivo T cell engineering is feasible and will produce more efficacious CAR-T cells with distinct features, reducing cost and increasing access. The work will be conducted at Stanford University School of Medicine, supported by a multidisciplinary team.

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