IMV102, an in vivo BCMA-targeting CAR-T therapy, achieves durable tumor control in multiple myeloma models

Introduction Autologous CAR-T therapy has achieved marked success in hematologic malignancies, yet its widespread use remains challenging due to complex manufacturing and high costs. To overcome these limitations, we developed the iMagic platform, a lentiviral-based in vivo CAR-T system composed of a mutated MxV glycoprotein (MxV-G-mut) and a T cell targeting module (TCM3). This platform enables selectively activation and transduction of T cells in vivo. Here, we evaluated the specificity, efficacy, and safety of IMV102, a lentivirus carrying the BCMA-targeting CAR as the gene of interest based on the iMagic platform, for the treatment of multiple myeloma in preclinical models. Methods The transduction specificity and efficiency of IMV102 was assessed using tumor cell lines (Jurkat, H929, and Raji) and primary human cells (hepatocytes and PBMCs). In vitro cytotoxicity and IFN-gamma secretion were measured following co-culture with target cells. In vivo efficacy was assessed in two separate models, H929-Luc or MM1.S-Luc xenografted MHC-I/II-DKO immunodeficient mice reconstituted with human PBMCs. Tumor burden, body weight, CAR-T expansion and plasma IFN-gamma levels were monitored per schedule. Results After coincubation with IMV102, BCMA-CAR expression was detected on Jurkat T cells, while it showed significantly lower levels in Raji or NCI-H929 cells. Importantly, IMV102 coincubation resulted in negligible CAR expression on primary human hepatocytes. In PBMCs, IMV102 efficiently transduced T cells with similar transduction ratio on CD4 and CD8 cells and showed negligible off-target B cell transduction. IMV102-generated CAR-T cells displayed potent cytotoxicity against BCMA-positive tumor cells and secreted significant levels of IFN-gamma. Furthermore, intravenous administration of IMV102 at dose of 5e6 TU/mice showed potent and durable tumor inhibition all through the over 50 days observation periods in both the NCI-H929 xenografted model and the MM1.S xenografted model. And the antitumor efficacy was accompanied by robust CAR-T generation and expansion, as well as IFN-gamma release. Treatment was well tolerated, with no significant weight loss observed. Conclusions IMV102 enables efficient and selective in vivo generation of functional BCMA CAR-T cells, resulting in potent and durable antitumor activity in multiple myeloma models. These results pave the way for further clinical investigation.