Neeli et al. showed that an i.m.-electroporated DNA vaccine encoding the plasma cell-unique/ MM-overexpressed orphan G protein-coupled receptor GPRC5D prevented s.c. myeloma growth in a murine MM model, and inhibited growth of established MM tumors when combined with anti-PD-1. This pattern of prophylactic and therapeutic efficacy was recapitulated in models of murine syngeneic hGPRC5D+ tumors treated with a human (h)GPRC5D-expressing adjuvanted nanoplasmid. Mono and combination therapy increased serum IgG, T cell, NK cell, DC, and macrophage levels in spleens and tumors, and induced hGPRC5D-specific T cells and antibodies.
Contributed by Paula Hochman
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.
Author Info: (1) Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA. neelipraveen@gmail.com. (2) Department of Medicine, Baylor College of Medicine, Houston, TX, 77030,
Author Info: (1) Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA. neelipraveen@gmail.com. (2) Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA. (3) Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA. (4) Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA. (5) Department of Urology, Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (6) Department of Urology, Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (7) Department of Pathology, Division of Hematopathology, Duke University Medical Center, Durham, NC, USA. (8) Department of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA. yong.li@bcm.edu.
