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- MxV-G is a novel fusogen for lentiviral packaging that achieves higher vector titers and enhanced transduction efficiency.
- The detargeted MxV-G mutant abolishes native receptor binding while preserving its fusogenic activity.
- With various TCMs, the MxV-G mutant selectively transduced T cells, yielding CAR-T cells in mice with efficiency and anti-tumor efficacy comparable to wild-type.
- TCM3, our in-house developed T cell-targeting module, is designed for specific binding, activation, and transduction of T cells.
- TCM3 achieved higher T cell transduction rates than αCD3/CD80/CD58 and αCD3/CD80 across various fusogen mutants.
- MxV-G-mut+TCM3 exhibited superior specificity profile on a panel of human normal or malignant cells
- TCM3 demonstrated more potent anti-tumor efficacy in mice model.
, /PRNewswire/ -- Immunofoco, a company dedicated to advancing cell therapies for solid tumors, announced that its independently developed, innovative lentiviral vector-based In Vivo CAR-T Technology Platform made a remarkable appearance at the 28th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT). This platform has broken the patent barriers in this field, achieving significant in-vitro and in-vivo specificity and efficacy, and providing a new strategy for tumor immunotherapy.
Novel Lentiviral Vector: Overcoming Patent Barriers with Superior Performance
Immunofoco's team developed a novel lentiviral vector pseudotyped with the MxV glycoprotein (MxV-G), demonstrating performance in generating CAR-T cells in vivo. Compared with the traditional VSV-G pseudotyped lentiviral vector, MxV-G pseudotyped vector not only enhances viral titer and transduction efficiency but also enables generated CAR-T cells to more effectively target and kill tumor cells. This novel envelope has good clinical application potential in both traditional ex vivo CAR-T and in vivo CAR-T.
AI-Driven Optimization: Successful Construction of Precision-Engineered Tropism-Modified Mutants
To eliminate the natural tropism of MxV-G and enhance its specificity, the team used an AI-driven protein model to successfully design and construct a mutant MxV-G. The mutated MxV-G eliminates the infectivity to non-T cells while retaining its membrane-fusion-mediating activity. By introducing different T-cell targeting modules, its infectivity to T cells is restored, achieving precise targeting and improving the safety and efficacy of treatment.
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Next-Generation T-Cell Targeting Molecules: Upgrading Specificity and Anti-Tumor Activity
To target T cells precisely, the team engineered multiple T-cell-targeting molecules (TCM). TCM3 demonstrated selective T-cell transduction with no off-target effects and outperformed αCD3/CD80/CD58 (MDF) and αCD3/CD80 in efficiency when paired with different membrane fusion protein variants. CAR-T cells generated by MxV-G-TCM3 showed high specificity across cell lines and reduced T-cell exhaustion markers, supporting sustained activity and improved tumor control. In mouse models, this combination exhibited significantly stronger in vivo anti-tumor efficacy compared to αCD3/CD80/CD58.
Dr. Hao Ruidong, Partner and Head of the R & D Center at Immunofoco, said, "CAR-T cell therapy has revolutionized cancer treatment, yet its complex manufacturing and high costs limit accessibility. Our novel in vivo CAR-T platform, powered by lentiviral technology, breaks foreign patent barriers in fusion proteins and T-cell targeting while showing strong in-vitro and in-vivo specificity and efficacy. With simpler manufacturing and lower costs, we aim to make this life-saving treatment accessible to more patients. Moving forward, we'll advance its clinical potential to maximize impact."
