DNA vaccines against GPRC5D synergize with PD-1 blockade to treat multiple myeloma

• Published in: npj vaccines Vol. 9; no. 1; pp. 180 - 14
• Main Authors: Neeli, Praveen, Maza, Perry Ayn Mayson A., Chai, Dafei, Zhao, Dan, Hoi, Xen Ping, Chan, Keith Syson, Young, Ken H., Li, Yong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-10-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/580; 692/699/67; Antibodies; Antigens; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cancer; Cells; Deoxyribonucleic acid; Disease prevention; DNA; FDA approval; Flow cytometry; Hematology; Immunotherapy; Infectious Diseases; Lymphocytes; Medical Microbiology; Multiple myeloma; Plasma; Plasmids; Proteins; Public Health; Spleen; Tumors; Vaccine; Vaccines; Virology
• ISSN: 2059-0105; 2059-0105
• DOI: 10.1038/s41541-024-00979-w

Multiple myeloma (MM), a hematological malignancy of the bone marrow, remains largely incurable. The orphan G protein-coupled receptor, GPRC5D, which is uniquely expressed in plasma cells and highly expressed in MM, is a compelling candidate for immunotherapy. In this study, we investigated the efficacy of a combination of DNA vaccine encoding mouse GPRC5D and PD-1 blockade in preventing and treating MM using the 5TGM1 murine model of MM. The mouse vaccine alone was effective in preventing myeloma growth but required PD-1 antibodies to inhibit established MM tumors. We next evaluated the prophylactic and therapeutic efficacy of a nanoplasmid vector encoding human GPRC5D in several murine syngeneic tumor models. Similar results for tumor inhibition were observed, as human GPRC5D-specific T cells and antibodies were induced by DNA vaccines. Taken together, these findings underscore the potential of GPRC5D-targeted DNA vaccines as versatile platforms for the treatment and prevention of MM.