A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity

长效白细胞介素-7(rhIL-7-hyFc)可增强CAR-T细胞的扩增、持久性和抗肿瘤活性。

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作者:Miriam Y Kim ,Reyka Jayasinghe ,Jessica M Devenport ,Julie K Ritchey ,Michael P Rettig ,Julie O'Neal ,Karl W Staser ,Krista M Kennerly ,Alun J Carter ,Feng Gao ,Byung Ha Lee ,Matthew L Cooper ,John F DiPersio

Abstract

Chimeric antigen receptor (CAR) T cell therapy is routinely used to treat patients with refractory hematologic malignancies. However, a significant proportion of patients experience suboptimal CAR T cell cytotoxicity and persistence that can permit tumor cell escape and disease relapse. Here we show that a prototype pro-lymphoid growth factor is able to enhance CAR T cell efficacy. We demonstrate that a long-acting form of recombinant human interleukin-7 (IL-7) fused with hybrid Fc (rhIL-7-hyFc) promotes proliferation, persistence and cytotoxicity of human CAR T cells in xenogeneic mouse models, and murine CAR T cells in syngeneic mouse models, resulting in long-term tumor-free survival. Thus, rhIL-7-hyFc represents a tunable clinic-ready adjuvant for improving suboptimal CAR T cell activity.

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