Development of CMV-CD19 bi-specific CAR T cells with post-infusion in vivo boost using an anti-CMV vaccine

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Abstract

Adoptive transfer of in vitro expanded, chimeric antigen receptor (CAR)-redirected CD19-specific T cells can induce dramatic disease regression in patients with leukemia and lymphomas. However, the full potential of this emerging modality is hampered in some cancer settings by a significant rate of therapeutic failure arising from the attenuated engraftment and persistence of CAR-redirected T cells, and tumor relapse following adoptive transfer. Here, we discuss an advanced strategy that facilitates post-infusion in vivo boosting of CAR T cells via CMV vaccination, to mediate durable remission of B cell malignancies by engrafting a CAR molecule onto a CMV-specific T cell. We also discuss a feasible and unique platform for the generation of the CMV-CD19CAR T cells for clinical application. This new approach would overcome multiple challenges in current CAR T cell technology including: short T cell persistence, limited duration of response, and inability to re-stimulate T cells after relapse or persistent disease.

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Wang, X., Diamond, D. J., Forman, S. J., & Nakamura, R. (2021, November 1). Development of CMV-CD19 bi-specific CAR T cells with post-infusion in vivo boost using an anti-CMV vaccine. International Journal of Hematology. Springer Japan. https://doi.org/10.1007/s12185-021-03215-6

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