The Nuclear Speckles Protein SRRM2 Is Exposed on the Surface of Cancer Cells

The membrane composition of extracellular vesicles (EVs) largely reflects that of the plasma membrane of the cell of origin. We therefore hypothesized that EVs could be used for immunizations to generate monoclonal antibodies against well-known tumor antigens but possibly also against hitherto unknown tumor-associated target molecules. From an immunization experiment, we obtained a monoclonal antibody specific for SRRM2, an RNA-binding protein involved in splicing and a major component of nuclear speckles. Here, we used this antibody to demonstrate that SRRM2 is exposed on the surface of most cancer cell lines from various entities and, even more important, on cancer cells in vivo. Moreover, we demonstrated that SRRM2-specific CAR-T cells are functional in vitro and in vivo. Collectively, we identified SRRM2 as a promising new target molecule exposed on the cancer cell surface and showed that our SRRM2-specific antibody can be used as a basis for the development of new targeted cancer therapies.