Abstract 277: IMV102, an <i>in vivo</i> BCMA-targeting CAR-T therapy, achieves durable tumor control in multiple myeloma models.

Abstract 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-γ 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-γ 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-γ. 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-γ 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. Citation Format: Yantao Li, Shuangshuang Zhang, Xiaojiang Fan, Zhenggang Jiang, Ruidong Hao, Minmin Sun. IMV102, an in vivo BCMA-targeting CAR-T therapy, achieves durable tumor control in multiple myeloma models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 277.