Breakthrough in Solid Tumor CAR-T Therapy: Xiankangda Life Sciences Publishes Novel IL-15-Inducible TRUCK Platform in Molecular Therapy

Recently, Shenzhen Xiankangda Life Science Co., Ltd. (hereinafter referred to as "Xiankangda Life") has made significant progress in the research of CAR-T cell therapy for solid tumors. The research paper titled **"Building a novel TRUCK by harnessing the endogenous IFN-gamma promoter for cytokine expression"** was successfully accepted and published by the international authoritative academic journal **Molecular Therapy**. This marks a global breakthrough for Xiankangda Life in the field of cell therapy, demonstrating its strong technical innovation capabilities and industry leadership while providing peers with new scientific perspectives and experimental methods, which is expected to accelerate the development of cell-based drugs.

Currently, CAR-T therapy has achieved remarkable success in the treatment of hematological tumors, but it still faces many challenges in the treatment of solid tumors. Although many researchers have attempted to enhance the killing ability of CAR-T cells by having them secrete cytokines, the risks associated with continuous cytokine secretion have limited further clinical application.

In this study, the research team adopted HDR-mediated gene knock-in technology to innovatively introduce exogenous IL-15 into the 3'-UTR region of the endogenous IFN-γ gene, using the endogenous IFN-γ promoter to regulate the expression of exogenous IL-15. Experimental verification showed that the expression of IFN-γ is precisely regulated by TCR signaling, and the insertion of exogenous IL-15 does not affect the expression of endogenous IFN-γ. This precise and timely regulation can effectively reduce the risks associated with continuous cytokine expression. Consistent data from in vivo and in vitro experiments indicate that IL-15 expression driven by the IFN-γ promoter significantly enhances the anti-tumor activity of CAR-T cells, thus validating the effectiveness of IL-15 expression in enhancing the anti-tumor function of CAR-T cells.

In addition, this research delves into key technologies such as gene editing and gene transduction, which are important foundations of Shenzhen Xiankangda Life Science Co., Ltd.'s core technology platform—the R-Star technology platform. The R-Star technology platform is an induction expression system based on gene editing technology that enables simultaneous editing of multiple genes mediated by one HDR. It can precisely induce cytokine secretion or functional protein expression in cells, thereby significantly enhancing the anti-tumor activity of CAR-T cells.

Ma Liya, Head of Shenzhen Xiankangda Life Science Co., Ltd.Stated: "As the only research unit, Xiankangda Life Sciences being able to publish the latest research findings in *Molecular Therapy* is the result of the collective efforts of all the team members. Currently, CAR-T cell therapy for solid tumors has encountered a bottleneck. This technology proposes an effective solution that not only significantly enhances the efficacy of CAR-T cell therapy but also greatly improves its safety, bringing new hope and possibilities to the field of cell therapy for solid tumors. At present, we are actively advancing the clinical research process of the R-Star platform products to further verify their excellent performance in future clinical practice. More importantly, this technology can significantly reduce the cost of formulation preparation, thereby greatly improving the affordability of clinical applications. We have very high expectations and confidence regarding the future market entry of solid tumor CAR-T products and the benefits patients will gain from them."

Shenzhen Xiankangda Life Science Co., Ltd. is a high-tech enterprise focused on the research and industrialization of cell immunotherapy for solid tumors. The company has developed two mainstream cell therapy technologies: T cells (including CAR-T and CAR-iT) and NK cells (including PANK and CAR-NK). Through independent research and development, Xiankangda Life has created three proprietary technology platforms: Trans-CAR, Boost-CAR, and R-Star, as well as two process platforms targeting NK cells: hNK.LV and FCF-NK. Currently, the company has initiated clinical research on CAR-T and PANK for solid tumors in multiple Class III hospitals in China, with preliminary data showing controllable safety and promising clinical efficacy.

Molecular Therapy is an international journal characterized by comprehensive research in medicine, bioengineering, and applied microbiology. It is a leading research journal in the fields of gene transfer, vector development and design, stem cell manipulation, genes, peptides, proteins, oligonucleotides, and cell-based therapeutic development to correct genetic and acquired diseases, vaccine development, preclinical target validation, safety/efficacy studies, and clinical trials. It is dedicated to promoting scientific advancements in genetics, medicine, and biotechnology, publishing significant peer-reviewed research, cutting-edge reviews, and commentary articles. Molecular Therapy's 2022 impact factor is 12.4.

Paper link:https://www.sciencedirect.com/science/article/pii/S152500162400399X