Scientific Insights on Tumor Therapeutics: Advancements in CAR-T Cell Therapy and Functional Peptides

October 23–25, the 12th China (Taizhou) International Medicine Expo was held at the China Medical City Exhibition Center in Taizhou.

Held in the historic city of Taizhou and backed by China Medical City, a national-level high-tech zone dedicated to the pharmaceutical industry, this edition of the Medical Expo is hosted by the China Chamber of International Commerce and the China Association of Chinese Medicine. It is organized by the Taizhou Municipal People’s Government and the Jiangsu Provincial Branch of the China Council for the Promotion of International Trade. Supporting organizations include the Chinese Medical Association, the Chinese Pharmaceutical Association, the National Institutes for Food and Drug Control, the China Institute of Veterinary Drug Control, as well as the Jiangsu Provincial Development and Reform Commission, Department of Science and Technology, Department of Industry and Information Technology, Department of Human Resources and Social Security, Department of Commerce, Health Commission, Administration for Market Regulation, Medical Products Administration, and Administration of Traditional Chinese Medicine.

Themed “Focusing on the Industry Frontier and Promoting Innovative Development,” this edition of the Medical Expo featured policy seminars, high-level industry forums, cutting-edge technology promotions, innovative product showcases, talent exchanges, and roadshow events. Leveraging Taizhou’s strategic geographic advantages as a key transportation hub, along with the policy support and resource strengths of China Medical City in Taizhou, the event presented a dynamic series of scenes highlighting pharmaceutical innovation and entrepreneurship, collectively painting a vivid picture of rapid, day-by-day progress driven by a sense of urgency.

Notably, the 4th China Conference on Regenerative Medicine and Biotechnology was also held at the China Medical City Exhibition Center during the expo. Researchers from scientific institutes, universities, hospitals, investors, and leaders in biotechnology and pharmaceutical companies from around the world gathered to discuss hot topics in the medical field. The following are excerpts from the forum:

(The following content is compiled from the speech “Current Status and Challenges of CAR-T Cell Therapy for Solid Tumors” delivered by Feng Zhenqing, Doctoral Supervisor at Nanjing Medical University, Director of the Medical Publishing Department, and Director of the Key Laboratory of Antibody Technology under the National Health Commission.)

CAR-T Cell Therapy: A Growing Topic of Discussion Amid Continuous Breakthroughs in Hematologic Malignancies in Recent Years

From the perspective of the company's R&D project pipeline layout, Currently, overseas companies developing CAR-T cell therapies primarily focus on the targets CD19 and BCMA; however, there is also significant development of other targets such as CD22, MUC16, CD123, CD171, and CS1, most of which have entered clinical trial stages, with indications predominantly being hematologic malignancies;

Currently, domestic targets are primarily focused on CD19; however, some companies have also made strategic layouts in the fields of BCMA, CD20, GPC3, CDK69, and CLDN8.2. China currently has two officially approved CAR-T cell products on the market, but most remain in the clinical research stage, with indications predominantly for hematologic malignancies.

In terms of the number of clinical trialsCurrently, the United States ranks first and China ranks second. The top ten regions globally in terms of the number of clinical trials are California, Texas, Pennsylvania, New York, Beijing, Massachusetts, North Carolina, Florida, Zhejiang Province, and Guangdong Province.

From the Perspective of Global Clinical Trial Development Stages, with most clinical trials in both China and the United States currently at Phase I and Phase II. From the perspective of patent cooperation networks, Chinese CAR-T cell patents lack collaboration and international layout, resulting in a marginal position within the global R&D network. It is evident that the increasing number of clinical studies on CAR-T cell therapy products presages the emergence of a growing array of such therapies in the future.

Although CAR-T cells have achieved breakthrough progress in the treatment of hematologic malignancies, there are still many challenges in treating solid tumors.

1. Heterogeneity of tumor antigens/antigen escape.To address this, the challenge of antigen heterogeneity can be overcome by simultaneously targeting multiple tumor antigens, introducing adaptor factors, and designing CAR-T cells that secrete BiTEs.

Second, the issue of impaired CAR-T cell homing.To address homing barriers, strategies include local infusion of CAR-T cells, delivery of CAR-T cells to tumor sites via implantable biomaterials, and the use of CAR-T cells expressing chemokine receptors. Furthermore, promoting Runx3 gene expression can enhance CAR-T cell accumulation and homing within tumor tissues, thereby inhibiting tumor growth.

Third, the issue of the immunosuppressive tumor microenvironment, which can be addressed by blocking immunosuppressive signals, reducing immunosuppressive cells and factors, modulating metabolism, and inhibiting the expression of hypoxia-inducible factors.

In addition to the aforementioned issues, challenges such as off-target effects and CAR-T cell toxicity remain; these can be addressed through strategies including the design of SynNotch CARs, small-molecule “on/off switches,” and gene editing.

In summary, although CAR-T cell therapy has developed rapidly, there are still issues that need to be optimized, and relevant research requires extensive exploration and accumulation. Chinese CAR-T cell products, which are currently showing strong development momentum, are in the process of commercial translation and are expected to achieve breakthrough results in the field of solid tumor treatment. Despite the many challenges currently facing CAR-T therapy, its future prospects are promising.

(The following content is compiled from the lecture “Regulatory Mechanisms of Hypoxia-Inducible Factor (HIF) on Cancer Stem Cells” delivered by Professor Lu Haiquan, a doctoral supervisor at Shandong University.)

Tumorigenesis and progression constitute a complex process influenced by multiple factors, among which alterations in the tumor microenvironment play a significant role.

Hypoxia is considered one of the most critical factors in the tumor microenvironment. Under hypoxic conditions, tumor cells adapt to this adverse environment through various cellular regulatory mechanisms, thereby enhancing their resistance and survival capacity. This phenomenon is relatively common in solid tumors.

Hypoxic stress can regulate tumor angiogenesis and suppress immune responses, playing a crucial role in promoting tumor progression and immune evasion. Hypoxia-inducible factor (HIF) is the core regulatory factor enabling tumor cells to adapt to the hypoxic microenvironment, exerting significant control over the process of tumorigenesis.

The existence of cancer stem cells is a key reason for tumor recurrence, metastasis, and ultimately threatens the lives of patients.A Study by Professor Lv Haiquan’s Team at Shandong University Reveals a Series of HIF-Mediated Regulatory Mechanisms in Cancer Stem Cells:

HIF promotes glutathione synthesis and alters the intracellular redox state by activating the expression of SLC7A11 and GCLM genes; HIF modulates the intracellular MAPK phosphorylation network by regulating the expression of DUSP9 and DUSP16 genes; HIF affects endoplasmic reticulum calcium release and alters the intracellular calcium signaling network by activating GSTO1 gene expression; HIF modifies chromatin structure by activating S100A10 gene expression. These pathways ultimately lead to increased expression of pluripotency factors, thereby enhancing the stemness of breast cancer cells.

Inhibiting HIF transcriptional activity is of significant importance for suppressing cancer stem cells, thereby enhancing the therapeutic efficacy against tumors. According to the latest research findings from Professor Lv Haiquan’s team, transcriptional co-factors of HIF play a crucial regulatory role in HIF transcriptional activity. The team recently identified multiple HIF transcriptional co-factors, such as NANOG and ANXA2. Disrupting the protein-protein interactions between these transcriptional co-factors and HIF can significantly inhibit HIF transcriptional activity.

Therefore, based on this mechanism, the efficacy, toxicity, and underlying mechanisms of HIF inhibition can be evaluated through computer simulations, cellular and molecular studies, and animal experiments. By screening appropriate drug libraries, compounds that disrupt the interaction between transcriptional co-factors and HIF proteins can be identified, thereby providing new and effective strategies for the treatment of cancer.