Construction and Expression Analysis of CAR Molecules Co-expressing NK Cell Engager

Cancer immunotherapy has significantly advanced in recent years, with Chimeric Antigen Receptor T-cell therapy (CAR-T) therapy at the forefront. Although multiple CAR-T therapies targeting hematological malignancies have received regulatory approval, the formation of CAR-T-resistant tumor cell populations due to tumor antigen downregulation remains a critical factor affecting the success of immunotherapy. Additionally, CAR-T therapy has shown limited efficacy in solid tumors clinical trials. Combining therapeutic strategies to enhance the effectiveness and safety of CAR-T cell therapies is an inevitable trend for future development. As a branch of immune cell-targeted therapy, cell engagers link two different cell types via a tumor-associated antigen (TAA)- targeting component and an effector cell recognition component. These engagers selectively attack and destroy targeted tumor cells, demonstrating immense potential and broad clinical prospects. This study constructed a molecular framework for co-expressing Natural Killer (NK) cell engagers with CAR molecules and validated their expression. This approach enables adoptive cells to target BCMA+ tumors while secreting cell engagers, conferring NK cells with the ability to target GPRC5D+ tumor cells through bispecific antibodies. Furthermore, the bispecific antibody crosslinker IL-15 promotes NK cell proliferation and survival, opening new avenues for tumor immunotherapy.