Dr. Yan

Dr. Chuan Yan
Emerging Research Grant
– Rhabdomyosarcoma

Massachusetts General Hospital

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Optimizing CAR T cell immunotherapy for pediatric rhabdomyosarcoma

Dr. Chuan Yan discusses the innovative science made possible by the PCRF Emerging Research Grant. Your gifts make progress possible.

Combination chemotherapies have revolutionized the treatment of pediatric rhabdomyosarcoma (RMS). Yet, cure rates have largely remained stagnant since their implementation. Recent clinical successes with two independent pediatric RMS patients using chimeric antigen receptor (CAR) T cells suggests opportunities to exploit immunotherapy in RMS. However, CAR T cell mechanisms and efficacy are poorly understood in pediatric RMS. Here, we demonstrated robust expression of EGFR in RMS patients, and show that EGFR CAR T cells can slow RMS growth in zebrafish and mouse xenografts. Newer generation of CAR T cells can be engineered to express cytokines to enhance tumor infiltration and killing. By leveraging a novel zebrafish xenograft model that allows engraftment of human T lymphocyte and RMS, my work will systemically interrogate the effect of 29 cytokines in the context of enhancing EGFR CAR T cell efficacy in killing RMS. Aim 1 will investigate the effects of 29 inflammation associated cytokines on enhancing EGFR CAR T cell efficacy in pediatric RMS grown in immunocompromised zebrafish. Aim 2 will create cytokine-expressing EGFR CAR T cells optimized for killing pediatric RMS. Superior efficacy will be validated using both immunocompromised zebrafish and mice xenograft models. Together, this work will provide much-needed preclinical rationale for use of an optimized EGFR CAR T cell therapy for pediatric RMS and has high likelihood of future clinical translation.

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Some people say that children make up 10% of our cancer population, but they are 100% of our future! ~ Dr. Alex Huang, Case Western