Tiankeya: Pioneering TCR-T Cell Immunotherapy to Conquer Solid Tumors

When discussing TCR-T therapy in immunotherapy, CAR-T is inevitably brought up for comparison.

A commonality between TCR-T and CAR-T is that both enhance the ability of T cells to recognize and kill specific cancer cell antigens through genetic modification.

In contrast, CAR-T cells recognize only tumor surface antigens, which makes CAR-T therapy more suitable for hematologic malignancies characterized by the expression of specific surface antigens. In the treatment of solid tumors, CAR-T therapy faces current challenges due to the lack of such surface markers. TCR-T cells, however, recognize processed and presented antigens, thereby expanding the recognition scope to include intracellular tumor antigens, making them more likely to breach the defenses of solid tumors.

A study published in Science Translational Medicine in March 2016 showed that next-generation cellular immunotherapy may bring hope for overcoming brain cancer. This novel cellular immunotherapy significantly improved the survival rate of mice with brain cancer, with nearly 50% of the mice being completely cured.

In August 2016, Tiankeya was established. In fact, prior to the company’s founding, the entrepreneurial team had already been deeply engaged in immunotherapy for many years. The decision to establish the company in 2016 was driven by the following three core rationales.

First, unlike surgery, radiochemotherapy, and targeted therapy, immunotherapy represents a new-generation technological platform. In particular, the discovery of tumor-specific T-cell receptors (TCRs) has long been a technical bottleneck in this field. “By independently developing high-efficiency TCR deep-sequencing technology, the Tiankeya team has continuously refined and updated this approach with meticulous craftsmanship. Leveraging advances in bioinformatics and single-cell omics, they have established a unique high-throughput platform analogous to lead compound screening in traditional small-molecule drug development.”

Second, Tiankeya’s team has remained at the international forefront of academic research in immunotherapy for many years, biding its time. “Seizing the opportunity highlighted by the success of CAR-T therapy, Tiankeya rapidly completed its technological reserves and international patent layout in areas such as target validation, T-cell modification, vectors, and cell production processes, positioning itself at the forefront of the commercialization of cellular immunotherapy.”

Third, among all current pharmaceutical R&D efforts, “immune cell therapies” are the only type of drug that can be directly translated from the laboratory to clinical practice. Due to the exploratory nature of R&D and the individualized characteristics of cell-based therapies, the success of immune cell therapy development relies more heavily on excellent clinical treatment protocols and experienced clinical teams than conventional drugs. In 2016, the founding team of Tiankeya built confidence through their practical experience and successes in CAR-T therapy, establishing a closed-loop system encompassing target selection, TCR screening, druggability assessment, industrial-scale manufacturing, clinical treatment trials, immunological monitoring in clinical studies, and regulatory filing for drug approval. The company aimed to enter a phase of rapid growth from its inception.

Subsequent developments have also validated Tiankeya’s assessments: from 2016 to 2019, Tiankeya successfully established R&D centers and clinical translation centers in Chongqing, Los Angeles, and North Carolina; completed TCR cloning and druggability assessment for multiple targets; secured the first batch of over 20 core international patents in cell therapy; and conducted preclinical studies for more than ten product pipelines. During this period, Tiankeya completed several rounds of financing, raising hundreds of millions of yuan.

According to reports, Tiankeya is an innovative R&D enterprise dedicated to advancing the development of immune cell therapies for solid tumors. Its operational headquarters is located at the Nansha Industry Incubator of Guangdong Medical Valley, where it has established a commercial-scale production and operations center spanning over 5,000 square meters. The decision to base its headquarters at the Nansha Industry Incubator of Guangdong Medical Valley was driven by Guangzhou’s leading position in talent, technology, medical resources, and policy support, as well as the Nansha District’s strategic geographic location and the superior services offered by Guangdong Medical Valley.

Additionally, Tiankeya has established R&D and clinical development centers in Los Angeles and the Research Triangle Park of North Carolina in the United States, as well as in Chongqing, China. Mr. Su Zhenbo, Chairman of Tiankeya, stated, “Initially, both scientific founders of Tiankeya were based in the United States. Due to the substantial need for top-tier talent during the early stages of R&D—a resource that was difficult to recruit domestically at the time—an R&D center was established in the U.S. Currently, Tiankeya’s R&D centers in China and the United States serve distinct yet complementary functions, working in synergy to advance technological development.”

Although Tiankeya has established R&D centers in both China and the United States, its focus on commercial translation remains in Asia. Therefore, Tiankeya has set up production facilities in China to carry out commercial-scale manufacturing and operations.

Tumor Control: Tiankeya Approaches the Complex Relationship Between Tumor Cells and the Immune SystemTumor cells are abnormal cells characterized by genetic mutations and the overexpression of oncogenes. These mutated or abnormally expressed proteins can be recognized by immune cells, enabling the immune system to identify and eliminate tumor cells.

Theoretically, immune cells can eliminate abnormal cells in real time, thereby eradicating tumors at their incipient stage. However, with human aging, the increased frequency of genetic mutations and the senescence of the immune system lead to a corresponding rise in tumor incidence. In advanced stages, the microenvironment established by mature tumors impairs the surveillance capability of T cells (a type of immune cell), allowing the tumors to evade immune-mediated killing.

Therefore, Tiankeya enhances the immune system’s ability to recognize and kill tumor cells by supplementing tumor-specific immune cells and equipping them with various specialized “warheads.” Su Zhenbo offered an analogy: “Defeating tumors requires coordinated operations between conventional forces and special forces. The conventional forces refer to the patient’s inherent immune protection against tumor cells, while the special forces refer to the engineered, empowered T cells, which possess the ability to specifically recognize tumor cells and remodel the tumor microenvironment.”

Tiankeya is the enterprise that provides “special forces.”

The field of tumor immunotherapy is an inevitable choice for Tiankeya.

First, the founding team of Tiankeya all possess backgrounds in immunology or bioengineering and have dedicated many years to researching the field of immunotherapy. For instance, Professor Li Qijing is an expert in molecular immunology who studied under Academician Mark Davis—the first scientist globally to discover the T-cell receptor (TCR)—at Stanford University. He has long been engaged in fundamental immunological research on T-cell antigen recognition. His textbook-level achievements established the minimal unit and rate-limiting steps of T-cell receptor recognition, introduced microRNA into the field of immunology during its nascent stage, and elucidated the regulatory mechanisms governing antigen recognition sensitivity during T-cell development. Meanwhile, he possesses extensive practical experience in translational medicine and collaboration with pharmaceutical companies, having led or participated in dozens of clinical trials in both the United States and China.

For another example, Professor Wang Pin is an expert in bioengineering who has conducted years of research on the engineering modification of immune regulation and targeted gene and drug delivery. He has published more than 70 papers in top international journals and holds four patents. The dendritic cell (DC)-targeted lentiviral vector system developed by his laboratory has been fully validated in Phase II clinical trials. The biotechnology companies he participated in during their early stages achieved significant success; notably, Immune Design was acquired by Merck after its listing on NASDAQ.

Secondly, in terms of disease progression, Tiankeya believes that the next decade will be a golden era for cancer treatment and management. According to the report "Current Status and Trends of Cancer in China," the top five cancers causing death in China are currently lung cancer, gastric cancer, liver cancer, esophageal cancer, and colorectal cancer, in that order. Among these, lung cancer accounts for the highest proportion of cancer-related deaths, at 21.68%. Public data indicates that cancer accounts for 16% of all deaths globally, making it a leading cause of death worldwide. "We feel fortunate because we are striving to address current unmet medical needs, working hard to manage cancer and save lives," remarked Su Zhenbo.

Finally, from a commercial perspective, unmet medical needs represent a significant opportunity. In recent years, global cancer incidence and mortality rates have continued to rise, with an estimated 21 million new cancer cases expected by 2030. In China, the number of individuals diagnosed with cancer within the past five years who are still alive is approximately 7.49 million, resulting in an overall five-year cancer prevalence rate of 556 per 100,000 people. Based on an estimated treatment cost of RMB 300,000 and a treatment penetration rate of 10%, the potential market size for CAR-T/TCR-T therapies in China exceeds RMB 200 billion.

Based on the above considerations, Tiankeya, with a mission to conquer cancer, has completed preclinical development of more than ten product pipelines. The main indications cover various tumors such as advanced recurrent and metastatic cervical cancer, nasopharyngeal cancer, head and neck cancer, lung squamous cell carcinoma, colorectal cancer, ovarian cancer, and brain cancer.

Currently, Tiankeya is collaborating with renowned institutions such as Sun Yat-sen University Cancer Center, the Institute of Cancer Research of the Third Military Medical University of the Chinese PLA, West China Hospital, and Beijing Tiantan Hospital to conduct translational clinical research and human clinical trials. Meanwhile, three of Tiankeya’s pipeline candidates will simultaneously undergo registrational clinical studies in the United States, covering multiple indications.

Since its inception, Beijing Tiankeya Biotechnology Co., Ltd. has secured hundreds of millions of yuan in financing. The company is highly favored by investment institutions due to its three core competencies: a solid scientific foundation and technological platform, an excellent execution team with rapid research advancement, and a leading position in a high-demand field.

A solid scientific foundation is essential for biopharmaceutical development. Su Zhenbo stated, “As of the end of 2019, Tiankeya had over 102 full-time employees, more than 40% of whom held doctoral degrees.” The majority of Tiankeya’s R&D team hail from top-tier institutions such as Stanford University, MIT, Duke University, Caltech, the University of Southern California, and UT Southwestern Medical Center, while other members come from internationally renowned pharmaceutical companies including Johnson & Johnson, Novartis, Pfizer, and Roche, bringing extensive experience in manufacturing, management, and clinical development. This concentration of top talent has ensured a robust foundation for Tiankeya’s growth.

In terms of its technological platforms, Tiankeya’s three core technical platforms consist of a cloning and assembly platform for tumor antigen-specific TCRs, a gene engineering platform based on T-cell biological characteristics, and an industrial-scale, clinical-grade viral transgenic vector production platform.

“The technological barriers to next-generation immune cell therapies are high, with few companies or teams worldwide focusing on this field. Our technology platform is at the forefront globally. For example, our TCR cloning platform and assembly verification technology enable the efficient discovery of TCRs and the completion of functional validation in a short time and at a low cost. Furthermore, our advanced immune cell engineering and viral gene engineering technologies allow for the high-efficiency loading of elements that counteract tumor immunosuppression or address tumor heterogeneity into immune cells, thereby achieving synergistic therapeutic effects,” introduced Su Zhenbo.

Tiankeya believes that another reason it is favored by investment institutions is its highly efficient execution team. “Since the company’s establishment, the team has completed international patent layout within two years and continuously advanced clinical progress. This also demonstrates the team’s execution capability and output efficiency.”

“The final point is the surging popularity of tumor immunotherapy, which has attracted significant attention from investment firms. More importantly, Tiankeya is at the forefront in this field. In fact, few companies can achieve all three of these strengths, which constitute Tiankeya’s core competitiveness.”