MUC1 as a target for CAR ‐T therapy in head and neck squamous cell carinoma

Identified the expression of MUC1 is higher in head and neck squamous cell carcinomas than non ‐neoplastic tissues. Construct the second‐generation CAR‐T cell (CAR‐MUC1 T cell) and the fourth‐generation CAR‐T cell (CAR‐MUC1‐IL22 T cell) structure, respectively, and verify the function of different T cells to target tumors in vitro and in vivo. Since IL22 can upregulate the exp ression of MUC1, the fourth‐generation CAR‐T can kill HNSCC cells more effectively. AbstractThe modification of chimeric antigen receptor (CAR) endowing T cells with tumor ‐specific cytotoxicity induces antitumor immunity. However, the structural characteristics of solid tumors, the loss of specific antigens, and the strong immunosuppressive environment are challenges to treat solid tumors with CAR‐T therapy. The purpose of our study was to find and verify the pot entials of CAR‐T therapies for patients with head and neck squamous cell carcinoma (HNSCC). First, we selected MUC1 as our research target and verified its differential expression in cancer tissues and adjacent non‐neoplastic tissues (ANNT). Next, we constructed a second‐generation CAR and val idated the cytotoxic function in vitro. In our study, we found that exogenous addition human IL22 recombinant protein could increase the MUC1 expression and enhance the function of T cells. In addition, we constructed a fourth‐generation CAR that secretes IL22. Finally, we verified the antitumor f unction of two different ...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research