Immunofoco, a Shanghai-based biotechnology company focused on advancing cell therapies for solid tumors, presented groundbreaking data on its novel lentiviral vector-based In Vivo CAR-T Technology Platform at the 28th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT). The platform represents a significant advancement in the field, breaking patent barriers while demonstrating impressive in vitro and in vivo specificity and efficacy.
Novel MxV Glycoprotein Enhances Vector Performance
At the core of Immunofoco's innovation is a lentiviral vector pseudotyped with the MxV glycoprotein (MxV-G), which has shown remarkable performance in generating CAR-T cells in vivo. Compared to traditional VSV-G pseudotyped lentiviral vectors, the MxV-G pseudotyped vector delivers multiple advantages: higher viral titers, enhanced transduction efficiency, and improved tumor-killing capacity of the resulting CAR-T cells.
The technology has demonstrated promising clinical application potential for both conventional ex vivo CAR-T manufacturing and the more innovative in vivo CAR-T approach, where T cells are engineered directly within the patient's body.
AI-Driven Engineering Creates Precision-Targeted Vectors
To enhance specificity and safety, Immunofoco's research team employed AI-driven protein modeling to design and construct a mutant version of MxV-G. This engineered variant successfully eliminates infectivity toward non-T cells while preserving its critical membrane fusion activity.
The mutated MxV-G represents a significant advancement in vector targeting. By introducing specialized T-cell targeting modules, the researchers restored the vector's ability to infect T cells specifically, thereby achieving precise targeting while improving both safety and efficacy profiles.
Next-Generation T-Cell Targeting Technology
A key component of the platform is Immunofoco's proprietary T-cell targeting molecule, TCM3. This in-house developed module is specifically designed for selective binding, activation, and transduction of T cells.
In comparative studies, TCM3 demonstrated superior performance:
- Higher T-cell transduction rates compared to alternative approaches using αCD3/CD80/CD58 and αCD3/CD80 combinations
- Selective T-cell transduction with minimal off-target effects
- Enhanced specificity across multiple human cell lines, both normal and malignant
- Reduced expression of T-cell exhaustion markers, supporting sustained anti-tumor activity
The combination of mutant MxV-G with TCM3 produced CAR-T cells that exhibited significantly stronger anti-tumor efficacy in mouse models compared to cells generated with other targeting approaches.
Implications for CAR-T Accessibility
"CAR-T cell therapy has revolutionized cancer treatment, yet its complex manufacturing and high costs limit accessibility," said Dr. Hao Ruidong, Partner and Head of the R&D Center at Immunofoco. "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."
The platform's simplified manufacturing approach could potentially reduce production costs significantly, addressing one of the major barriers to widespread adoption of CAR-T therapy. Current CAR-T manufacturing requires complex ex vivo cell processing, contributing to treatments that can cost hundreds of thousands of dollars per patient.
Technical Achievements Highlight Platform Potential
The technical data presented at ASGCT demonstrated several key advantages of Immunofoco's platform:
- The detargeted MxV-G mutant successfully abolishes native receptor binding while preserving fusogenic activity
- When combined with various targeting modules, the MxV-G mutant selectively transduces T cells, yielding functional CAR-T cells in mice
- The efficiency and anti-tumor efficacy of these cells are comparable to those generated with wild-type vectors
- The MxV-G-mut+TCM3 combination exhibited a superior specificity profile across a panel of human cells
These achievements suggest that Immunofoco's platform could potentially address several limitations of current CAR-T approaches, including manufacturing complexity, cost barriers, and targeting precision.
Future Development Path
Immunofoco plans to advance the platform toward clinical applications, with the goal of making CAR-T therapy more accessible to cancer patients worldwide. The company's innovative approach to in vivo CAR-T generation could potentially transform how these therapies are delivered, moving from complex manufacturing processes to more direct treatment approaches.
As solid tumors remain a significant challenge for current CAR-T therapies, Immunofoco's focus on advancing cell therapies specifically for solid tumors represents an important direction for the field. The enhanced specificity and reduced exhaustion profiles of CAR-T cells generated through their platform may prove particularly valuable in addressing the hostile microenvironment often found in solid tumors.
The presentation at ASGCT marks an important milestone for the company as it works to translate these promising preclinical findings into clinical applications that could benefit cancer patients.
