Bio: Yang Wei, Professor/doctoral supervisor, National science and technology leader, Executive director of Chinese Society of Toxicology/Chairman of the Society of Toxicology of Traditional Chinese Medicine and Natural Medicine, Chief scientist/Chairman of Guangdong LEWWIN Pharmaceutical Research Institute Co., LTD., Director of Guangdong Key Laboratory of Non-Clinical Evaluation and Research of Drugs.

Abstract: In recent years, cell therapy has demonstrated groundbreaking potential in the field of solid tumors. However, compared to hematologic malignancies, its application in solid tumors faces unique challenges such as immunosuppressive microenvironments, target antigen heterogeneity, and low delivery efficiency. This report systematically explores the development progress of mainstream products including CAR-T, TCR-T, TIL, and NK cells, focusing on key scientific issues in non-clinical research, and analyzes optimization strategies through representative case studies. After years of development, cell therapies have become increasingly widely used in solid tumor treatment, with different cell types exhibiting distinct characteristics. CAR-T cells, engineered to target tumor surface antigens, are limited in solid tumors due to antigen escape, immunosuppressive microenvironments, and tumor heterogeneity. TCR-T cells, which recognize intracellular antigen peptide-MHC complexes, expand the target range by identifying endogenous tumor protein fragments and have achieved breakthroughs in treating solid tumors with multiple TCR-related targets. TIL therapy leverages the natural anti-tumor activity of tumor-infiltrating lymphocytes, demonstrating durable responses in metastatic solid tumors. Additionally, various novel T-cell immunotherapies have brought further breakthroughs in solid tumor treatment. NK cells, with their innate killing properties that do not require antigen pre-sensitization, show unique advantages in immune "cold" tumors such as breast and ovarian cancers. Novel cell therapy products require comprehensive non-clinical studies to conduct "proof-of-concept" validation for potential clinical issues, identify treatment risks and outcomes, and provide critical data for clinical applications. The core considerations in non-clinical research for cell therapies include: (1) Pharmacodynamics Evaluation; (2) Safety Assessment; (3) Pharmacokinetic Characteristics;(4) Immunogenicity Risk. The author will share 2-3 case studies of different types of cell therapy products for solid tumors to explore practical issues in non-clinical research. Non-clinical research for solid tumor cell therapies requires a comprehensive evaluation system that incorporates advanced technologies and assessment frameworks. By addressing key scientific issues and optimizing research strategies, non-clinical studies can provide robust support for the clinical translation of cell therapy products, ultimately improving their efficacy and safety in treating solid tumor.