Huida Bio's Immortalized DC-CTL Technology Addresses Key Limitations of CAR-T and Offers a Breakthrough in Solid Tumor Therapy

Immortalized DC-CTL technology is an innovative approach in the field of cellular immunotherapy, currently undergoing clinical research at the Chinese PLA General Hospital. This marks the first global clinical trial of this technology. To date, Phase I safety trials have been completed, with improvements in Quality of Life (QOL) scores observed in some patients. Efficacy studies are still ongoing.

VCBeat (WeChat ID: vcbeat) interviewed Professor Shao Yongping, who earned his Ph.D. in Molecular Biology from the University at Albany, State University of New York, and learned about the latest advances in the novel immortalized DC-CTL technology.

Professor Shao currently serves as the Chief Scientist at Beijing Huida Biotechnology Co., Ltd. (hereinafter referred to as “Huida Bio”). He has participated in more than ten major research projects both domestically and internationally, published nearly 40 papers in core journals such as Cancer Research and Immunity, and contributed to the compilation of the textbook Molecular Cell Biology, which was included in the National 13th Five-Year Plan for Higher Education.

It is reported that immortalized DC-CTL technology has overcome the long-standing bottlenecks hindering the advancement of immunology and immune cell-based anticancer therapies, holding promise for a definitive cure for cancer. This technology also demonstrates broad application prospects in combating diseases such as hepatitis B, HIV/AIDS, avian influenza, and Middle East Respiratory Syndrome (MERS).

Schematic Diagram of the Principle of Immortalized DC-CTL Technology

By using immortalized dendritic cell (DC) lines that are HLA-matched to the patient and express solid tumor-specific antigens or neoantigens, patient T cells are activated in vitro to undergo extensive expansion and differentiation into cytotoxic T lymphocytes (CTLs), predominantly composed of antigen-specific CD8+ T cells, thereby enabling targeted tumor killing.

First, the targets of immortalized dendritic cell (DC) technology are not restricted; both intracellular and extracellular targets can be recognized by DCs. This is due to the mechanism of action of DCs: upon encountering antigens, DCs directly capture them, process them into peptide fragments, present these fragments on the cell surface in conjunction with major histocompatibility complex (MHC) molecules, and thereby activate T cells to initiate an immune response.

Huida Bio is currently conducting clinical trials for lung cancer, targeting the intracellular protein MAGEA3, which is specifically expressed in lung cancer patient tissues. While CAR-T technology is ineffective against such targets, immortalized DC-CTL technology is not limited by whether the target is intracellular or extracellular, thereby enabling cell therapy using immortalized dendritic cell (DC) technology for this type of disease.

Second, immortalized DC-CTL technology eliminates the need to screen for “bullet” antibodies. Professor Shao explained, “With immortalized DC-CTL technology, there is no longer a need to screen antibody libraries. Instead, we directly clone the genes corresponding to proteins specifically expressed by tumors and insert them into dendritic cells (DCs).” This approach requires only the isolation of tumor-specific proteins from the patient’s cancer cells. By engineering DCs to express these same proteins, the technology can effectively “train” T cells to recognize and attack the corresponding tumor cells.

Third, compared with CAR-T technology, the most significant advantage of immortalized DC-CTL technology is that it leverages dendritic cells (DCs) to naturally stimulate T cells, rather than artificially inducing an immune response. This approach mimics the intracellular environment for T-cell expansion, thereby achieving higher efficiency. Professor Shao told reporters, “We can stimulate T-cell expansion by tenfold or even a hundredfold within a short period, significantly shortening the preclinical preparation time.”

Instead of directly engineering CAR-T cells, this approach modifies upstream dendritic cells (DCs), enabling the infusion of unmodified T cells back into the human body, which is safer and more effective.

Currently, while many institutions both domestically and internationally are engaged in dendritic cell (DC) immunotherapy, only a handful are working on immortalized DC immunotherapy. Professor Shao stated, “In China, there is only one research institution conducting academic-level research on immortalized DCs. We have not yet found a second organization that, like Huida Bio, has translated this technology into clinical development.”

Abroad, a French-Belgian joint venture is also advancing the clinical translation of immortalized dendritic cell (DC) technology. However, the company’s immortalized DC cells are not manufactured in-house; instead, they are “naturally immortalized DC cells” extracted from a patient with a rare disease.

The company’s subsequent procedures mirror those of Huida Bio: antigen genes are introduced to activate T cells, which are then infused back into the patient. However, as this is the only naturally immortalized cell line, all of the company’s R&D efforts revolve around this single line, offering only a single HLA match for therapy. Consequently, tumors that are not HLA-matched with this dendritic cell (DC) line cannot be treated. In contrast, Huida Bio’s immortalized DC cells are artificially engineered, and currently more than ten HLA-matched DC cell lines are available.

In 2016, U.S.-based Back Bay Partners stated that immortalized dendritic cell (DC) technology was an emerging innovation valued at over $100 million. Huida Bio was the first to enter this blue-ocean market.