CDH17 is a new approach to treating solid cancers
Chimeric antigen receptor (CAR) T cells can be remarkably effective in treating leukemias and lymphomas, but there are no successful immunotherapies for neuroendocrine tumors (NETs) and gastrointestinal cancers (GICs) yet.
Researchers at Penn Medicine have discovered that CAR-T cells directed to a tumor antigen, CDH17, a cell surface marker expressed on both NETs and GICs but also found on healthy tissues. The results from this study, the first to target CDH17 in neuroendocrine tumors.
In the study, published March 21 in Nature Cancer, researchers isolated a llama-derived nanobody, a small antibody, which led to the identification of CDH17 and targeting CDH17—which, in humans as in mice, is mainly expressed in the intestinal system—with CDH17CART cells eliminated gastric, pancreatic, and colorectal cancers in mouse models.
While CDH17 is also expressed in normal intestinal epithelial cells, the CDH17CART cells did not attack the normal cells, likely because the CAR-T cells cannot reach or bind to healthy tissue in the tight junction between normal intestine epithelial cells, creating a “masking” effect in healthy cells from CAR-T attack.
This opens avenues to explore a new class of tumor antigens that are also expressed in normal cells but protected by the CAR-T cell attack and is hopefully another important step in developing safer immunotherapies for solid tumors.
The CDH17CART cells may be particularly suitable for patients with solid tumors, and these findings motivate additional investigation of CAR-Ts.
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