npj Vaccines (Oct 2024)

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

  • Praveen Neeli,
  • Perry Ayn Mayson A. Maza,
  • Dafei Chai,
  • Dan Zhao,
  • Xen Ping Hoi,
  • Keith Syson Chan,
  • Ken H. Young,
  • Yong Li

DOI
https://doi.org/10.1038/s41541-024-00979-w
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 14

Abstract

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Abstract 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.