Development of a novel target module redirecting UniCAR T cells to Sialyl Tn-expressing tumor cells


Development of a novel target module redirecting UniCAR T cells to Sialyl Tn-expressing tumor cells

Loureiro, L.; Feldmann, A.; Bergmann, R.; Koristka, S.; Berndt, N.; Arndt, C.; Pietzsch, J.; Novo, C.; Videira, P.; Bachmann, M.

The development of antibody-based therapies has been driven by progress in the immune response field culminating in the development of chimeric antigen receptors (CARs) as a promising approach in cancer immunotherapy. Nevertheless, drawbacks associated with CAR T cell therapies include on-target off-tumor effects or severe toxicity. Recently, we developed a novel modular universal CAR (UniCAR) platform to increase clinical safety while maintaining the efficacy of CAR T cell therapy. UniCAR T cells are exclusively activated via a target module (TM) that allows the cross-link between UniCAR T cells and target cancer cells. Here, we describe a novel TM against the tumor-associated carbohydrate antigen sialyl-Tn (STn). The developed anti-STn TM efficiently activate and redirect UniCAR T cells to STn-expressing tumors in a highly efficient target-specific and target-dependent manner, promoting the secretion of pro-inflammatory cytokines, tumor cell lysis of breast and bladder cancer cells in vitro and of breast cancer cells in experimental mice. Additionally, PET-imaging shows that anti-STn TM is enriched at the tumor site representing the potential use of this TM in diagnostic imaging. Taken together, these data demonstrate the effective and potential use of this CAR T cell-derived modular system to target STn in different types of cancer.

Keywords: Immunotherapy; CAR T cell therapy; Sialyl-Tn (STn)

Permalink: https://www.hzdr.de/publications/Publ-27716
Publ.-Id: 27716