Shanghai Jiao Tong University Licenses Three In Vivo CAR-T Therapy Patents to Fengxun Bio for RMB 2 Million
Recently, the Advanced Industrial Technology Research Institute of Shanghai Jiao Tong University released an announcement on the conversion of scientific and technological achievements, announcing its intention to transfer“Specific Viral Envelope Proteins and Their Lentiviral Vectors and Applications” “A Specific Protein Degradation System and Its Application” “Recombinant Viral Particles”The rights to apply for three invention patents were transferred through related-party assignments. In this transaction, the transferee isNingbo Fengxun Biotechnology Co., Ltd., with the proposed transaction amount reaching2 million yuan。
All three patents are held byCai Yujia's TeamSpearheading R&D. Professor Cai Yujia has dedicated nearly 20 years to the fields of viral vector engineering and in vivo gene editing. He currently serves as a Researcher and Assistant Dean at the Institute of Systems Biomedicine, Shanghai Jiao Tong University, and as Deputy Director of the Shanghai Key Laboratory of Gene Editing and Cell Immunotherapy for Hematologic Diseases. Leveraging his pioneering virus-like particle (VLP) delivery technology, he founded BenDao Gene, achieving major breakthroughs including the world’s first clinical application of in vivo gene editing for antiviral therapy. Since 2017, his laboratory has been strategically positioning itself in this field.In Vivo CAR-T Cell Therapy, and foundedFengxun Bio。
Focus on Transfer Targets"In Situ Generation of CAR-T Cells"This cutting-edge immunotherapy technology specifically comprises viral envelope proteins that can specifically target T cells, recombinant lentiviral vectors with both T cell activation and co-stimulation functions, and a CAR protein degradation system designed to enhance the purity and safety of viral vectors. These three patents collectively form a complete “in vivo CAR-T” technology platform, which aims to directly convert ordinary T cells into tumor-targeting CAR-T cells within patients’ bodies through a single intravenous injection of engineered viruses. This approach holds promise for overcoming the bottlenecks of traditional CAR-T therapy, including high costs, lengthy production cycles, and complex manufacturing processes.
CAR-T cell therapy demonstrates significant application potential in the fields of oncology, autoimmune diseases, viral infections, and aging. However, existing CAR-T therapies face substantial technical and economic challenges. The traditional manufacturing process for CAR-T cells is complex, involving steps such as leukapheresis to collect T cells from patients, ex vivo transduction with VSV-G pseudotyped lentiviral vectors, expansion culture, and reinfusion. This process is time-consuming, often taking several weeks, and incurs high costs, which severely limits its widespread adoption. Achieving in vivo generation of CAR-T cells holds the promise of significantly reducing production costs and simplifying treatment protocols.
The process of viral infection of cells is typically initiated by the binding of viral surface membrane proteins to host cell surface receptors, which subsequently mediates the fusion of the virus with the cell membrane and injects the viral nucleic acid into the cell. Paramyxoviruses encode two key envelope proteins:Receptor-binding protein and fusion protein F,The latter is responsible for membrane fusion during viral contact with cells. Given this characteristic, the G protein of paramyxoviruses such as Nipah virus (NiV) can be engineered to enhance specific recognition of target cells. However, existing engineering approaches targeting the NiV G protein often suffer from insufficient viral titers and low targeting efficiency, limiting their potential for clinical translation.
The advantage of in vivo CAR-T therapy lies in its ability to simplify the manufacturing process and reduce costs. By editing T cells directly within the patient’s body, it avoids complex ex vivo manipulations, significantly shortening the treatment cycle and accelerating therapeutic delivery—a critical benefit for patients with rapidly progressing cancer. Furthermore, this therapy does not depend on the patient’s T cell status, making it suitable for a broader patient population, particularly those unable to provide sufficient healthy T cells. Meanwhile, as it eliminates the need to customize T cells for each individual patient, it facilitates large-scale production and distribution while reducing the risk of contamination.
However, in vivo delivery still faces off-target issues, primarily stemming fromNonspecificity of delivery systems, flaws in molecular structure design, and the impact of complex in vivo environments.For instance, delivery vectors may lack sufficient targeting specificity, leading to widespread distribution of drugs or gene-editing tools rather than concentrated action at specific sites. To overcome these challenges, enhancing the targeting specificity and transduction efficiency of vectors for T cells has become critical. Furthermore, controlling CAR expression levels is an important measure to ensure safety, aiming to mitigate cytokine release syndrome and other potential adverse effects.
Therefore, the teamDeveloped an Innovative "In Vivo CAR-T" Platform, aiming to address the high costs, complex manufacturing processes, and poor targeting associated with current CAR-T therapies, thereby promoting further development and clinical application in this field.
The core innovation of this technology platform lies in the synergistic design of three patents, which systematically addresses the challenges of in vivo CAR-T therapy inTargeting, Activation Efficiency, and Vector PurityTechnical bottlenecks in three key areas, forming a highly integrated, original solution with potential for clinical translation.
Precision Targeting: Remodeling the Viral Envelope for T Cell-Directed Delivery
In terms of viral targeting, the team overcame the limitations of traditional VSV-G envelope lentiviruses lacking cell specificity and innovatively utilizedEnvelope System of the Paramyxovirus Nipah Virus (Nipah virus), target molecules that recognize T cell surface markers (such as CD3 or CD4), such as scFv or DARPin, are precisely fused to their G proteins. This modification not only preserves the virus’s efficient membrane fusion capability but also confers high selectivity for T cells, significantly enhancing the precision of in vivo delivery and mitigating safety risks associated with non-specific infection.
High-Efficiency Activation: Fusion Protein Design for Simultaneous Delivery and Activation
In terms of T cell activation and transduction efficiency,The research team designedMultifunctional Fusion Protein, willCD58 (promoting T cell–antigen-presenting cell adhesion), anti-CD3 single-chain antibody (providing TCR activation signals), and CD86 (providing co-stimulatory signals) are integrated as a triad on the viral surface.This design achieves simultaneous “delivery + activation”: upon binding to T cells, the virus not only delivers the CAR gene but also immediately triggers the transition of T cells from a resting state to an effector state. Crucially, the team proposed and validated for the first time that CD86 is superior to the traditional CD80 as a costimulatory element, as it binds to the CD28 receptor more rapidly, thereby enabling more efficient and stable in situ generation of CAR-T cells within the complex in vivo environment.
Safety Enhancement: Targeted Degradation Technology to Mitigate Off-Target Risks of Carriers
In terms of safety and functional purity in vector production,The team discovered that if the CAR protein is expressed on the surface of producer cells during viral packaging, it becomes erroneously incorporated into the viral capsid. This causes the virus to preferentially bind to tumor cells in vivo and become “trapped,” severely compromising its transduction efficiency into T cells. To address this, they innovativelyIntroduction of Protein Degradation Tags(e.g., ZP1 or CPPLSS), during the viral production phase, free CAR proteins are selectively degraded to ensure that the surface of the final viral particles is “clean,” retaining only the functional proteins required for T-cell targeting. This strategy effectively circumvents CAR-mediated off-target adsorption, significantly enhancing the reliability of in vivo transduction and widening the therapeutic window.
The three patents center on the goal of “efficient, safe, and controllable in vivo CAR-T generation,” establishing a logically rigorous and mutually reinforcing technological closed loop across the three dimensions of delivery, activation, and quality control.
Currently, the research and development of in vivo CAR-T cell therapy is accelerating globally, with multiple companies and research institutions deploying different technical pathways aimed at achieving"Direct Generation of CAR-T Cells In Vivo"This disruptive goal.
As of early 2026, related technologies are primarily divided into two major directions: one involves permanent gene integration strategies based on viral vectors, aiming for long-term or even durable therapeutic effects; the other employs transient expression systems using mRNA-lipid nanoparticles (LNPs), emphasizing safety and the ability to administer repeated doses.
In the viral vector approach,Multiple platforms have entered the clinical stage. For example,Interius BioTherapeuticsINT2104, developed by (now part of Kite/Gilead), is the world’s first in vivo CAR-T therapy to enter clinical trials. It completed dosing of the first patient in 2024, utilizing a targeted lentiviral vector to deliver CD20 CARs without requiring ex vivo manipulation or lymphodepletion. Almost simultaneously,EsoBiotec(later acquired by AstraZeneca) launched an investigator-initiated trial (IIT) of ESO-T01 in China. This product utilizes nanobody-modified lentiviral vectors to target BCMA for the treatment of multiple myeloma, and preliminary positive data were announced in 2025. Furthermore,Umoja BiopharmaThe VivoVec™ platform is also highly representative—its lentiviral vectors are engineered to display activating molecules such as CD58 and anti-CD3 on their surface, enabling not only T-cell targeting but also the simultaneous delivery of co-stimulatory signals. Its CD19-directed candidate, UB-VV111, received FDA approval in 2024 to initiate Phase I clinical trials.
In contrast,mRNA-LNP Pathwaythen take a different approach.Capstan TherapeuticsCPTX-2309, developed by (acquired by AbbVie), employs targeted lipid nanoparticles (LNPs) to deliver CAR mRNA to CD8+ T cells. However, its indications focus on autoimmune diseases such as systemic lupus erythematosus rather than oncology, with Phase I clinical trials initiated in 2025. AndMyeloid TherapeuticsTaking this a step further, the CAR delivery target has shifted from T cells to myeloid cells (such as monocytes/macrophages), exerting antitumor effects by reprogramming the tumor microenvironment. Its MT-302 and MT-303 projects have demonstrated the potential to remodel the immune microenvironment in early-stage clinical trials.
Currently, no in vivo CAR-T products have been approved for market launch worldwide, with all pipelines remaining in the early stages of clinical exploration. Amidst global competition, domestic innovators are poised to secure a significant position in the next generation of cell therapy through original innovations and clinical translation across multiple dimensions, including mechanism design, targeting precision, and process control.