Anti‐tumor efficacy of human anti‐c‐met CAR‐T cells against papillary renal cell carcinoma in an orthotopic model

• DOI: 10.1111/cas.14835
• Publication Date: 2021-02-06T07:44:06Z
• Authors: Jun‐ich Mori; Keishi Adachi; Yukimi Sakoda; Takahiro Sasaki; Shunsuke Goto; Hiroaki Matsumoto; Yoji Nagashima; Hideyasu Matsuyama; Koji Tamada
• Keywords: Male; Receptors, Chimeric Antigen; T-Lymphocytes; Proto-Oncogene Proteins c-met; Xenograft Model Antitumor Assays; Antibodies; Kidney Neoplasms; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; 0302 clinical medicine; Antigens, Neoplasm; Mice, Inbred NOD; Cell Line, Tumor; Animals; Humans; Female; Immunotherapy; ORIGINAL ARTICLES; Carcinoma, Renal Cell; Cells, Cultured; Aged

AbstractChimeric antigen receptor (CAR)‐T cell therapy has shown salient efficacy in cancer immunotherapy, particularly in the treatment of B cell malignancies. However, the efficacy of CAR‐T for solid tumors remains inadequate. In this study, we displayed that c‐met is an appropriate therapeutic target for papillary renal cell carcinoma (PRCC) using clinical samples, developed an anti‐human c‐met CAR‐T cells, and investigated the anti‐tumor efficacy of the CAR‐T cells using an orthotopic mouse model as pre‐clinical research. Administration of the anti‐c‐met CAR‐T cells induced marked infiltration of the CAR‐T cells into the tumor tissue and unambiguous suppression of tumor growth. Furthermore, in combination with axitinib, the anti‐tumor efficacy of the CAR‐T cells was synergistically augmented. Taken together, our current study demonstrated the potential for clinical application of anti‐c‐met CAR‐T cells in the treatment of patients with PRCC.