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Immunoengineering

Immunoengineering - Poster Session B

Poster CC14 - Engineering hyper-migration of CAR T cells to enhance infiltration in solid tumors

Thursday, October 24, 2024
2:45 PM – 3:45 PM EST
Location: Exhibit Hall E, F & G

Introduction: Patient T cells modified with chimeric antigen receptors (CARs) have been clinically implemented with remarkable success in previously incurable cancers. However, despite its success in hematological malignancies, it has only shown modest efficacy in solid tumors which comprise the majority of cancers. Although the field has focused on enhancing CAR T persistence and the prevention of exhaustion in the tumor microenvironment (TME), as well as increasing the specificity of the CAR to various tumor antigens, less interest has been placed on the poor migration of CAR T cells through the stiff stromal matrix of the TME, where they can elicit their tumor-directed cytotoxicity.

Materials and

Methods: Here we engineered CAR T cells with a synthetic or intrinsic cytokine receptor, denoted as velocity receptor (VR), targeting several inflammatory cytokines which we have previously shown promote hypermigration in primary T cells through autocrine signaling. These modified T, or CAR-TV, cells are assessed for tumor infiltration and its correlation with cytotoxicity in various in vitro and in vivo models.

Results, Conclusions, and Discussions: CAR-TV cells enhanced cytotoxicity and induced higher secretion of effector molecules during coculture with various solid tumor-derived cell lines in vitro. Compared to M5 CAR T cells, CAR-TV cells enhanced infiltration and reduced tumor burden in several pre-clinical models. These results support the use and discovery of cytokine receptors that induce hypermigration of cellular therapies for improved efficacy in solid tumors.

Acknowledgements (Optional):