Nature: A Review of Cancer Cell Treatment Targets

The largest number of the rapandatives in the field ofimmunologyare cell therapyIn an article published on May 26th, reviewnature dating: the clinical landscape trial, the authors provide the latest information on cancer cell treatment pipelines and clinical trials, comparing the data as of March 2020 with those of the same period last yearcell therapy, refers to the use of certain cells with specific functions, using bioengineering methods to obtain and/or through in vitro amplification, special culture and other treatment, so that these cells have enhanced immunity, kill pathogens and tumor cells, promote tissue organ regeneration and body rehabilitation and other therapeutic effects, and then these cells are inducted into the human body, in order to achieve the purpose of treatment or mitigation of diseasescell therapy is divided intostem celltreatment andimmunocellular therapyThe classification of cell therapyimmunocellular therapy is of great interest, and its efficacy in the field of hematoma is remarkableHowever, because it is difficult for immune cells to immerse themin into large and dense solid tumors, its targeted lethal function is often inhibited by the physical tumor microenvironment,CAR-Ttherapy in solid tumors (liver cancer, lung cancer, prostate cancer,stomach cancer, rectal cancer, kidney cancer, etc.) temporarily encountered barriers of cancer cell therapy pipeline Pipeline Trends currently has 1,483 active therapies in the global cancer cell therapy pipeline, an increase of 472 compared to last year The number of inline antigen receptor T-cell (CAR-T) therapies increased the most among different cell therapies (290 this year and 164 in 2019), while new T-cells (such as CRISPR engineered T-cells or gamma-based T-cells) and other cell therapies (e.g macrophages-based therapies) increased to 49 and 56 (Figure 1), respectively Figure 1 Cancer Cell Therapy Pipeline Trends (Photo: Nature Reviews Drug Discovery) To improve understanding of the year-on-year growth in cell therapy (Figure 2), the authors reclassified cell therapy as an ethnotherapy or hosome (off-shelf) based on sources Most cell immunotherapy (667) in the study is essentially autologous However, the growth of all theotherapy in pre-clinical and clinical Phase I development was the largest in 2019, increasing by 73.8% and 90.9%, respectively Most of the stage II and subsequent stages of cell therapy have been developed in countries other than the United States and have not disclosed whether they are ethnotherapy or allogeneic therapy (Figure 3) It is worth noting that the previously listed allogeneic nalotimagene carmaleucel, which failed to improve disease-free survival in phase III clinical trials, was removed from the EU market by its manufacturer MolMed in October 2019 Figure 2 Comparison of cell therapies in "Allogenic" and "Self-Contained" or "Undisclosed Cell Origins" (Photo: Nature Reviews Drug Discovery) Figure 3 Analyzes the 2020 Cancer Cell Therapy Pipeline Patterns by Country and Research stage (Source: CRI IO Analytics and Global Data) Hemaanda and Solid Tumor Hotspots For better understanding of cancer cell therapy targets CD19 remains the leading target for hematomy cell therapy, but the number of treatments targeting B-cell maturation antigens (BCMA) or CD22 has almost doubled since last year Solid tumor cell therapy is the primary target of undisclosed tumor-related antigens (TAA), with a total of 65 active research projects In addition, the largest variations in TOP10 targets are Glypican 3 (GPC3) and prostate-specific membrane antigens (PSMA) This may be due to the high expression of GPC3 in children solid embryonic tumors (solid embryotumours) and adult liver cell carcinoma (which is very common in China) and the presence of high expression of PSMA in prostate cancer Figure 4 Major targets for hematoma and solid tumor cell therapy (Photo: Nature Reviews Drug Discovery) Clinical Trial development In published clinical data trials, most of the clinical Phase I or Phase II trials of solid and hema sorority have reached the primary endpoint and rarely report negative results (Figure 5) It is important to note that tumor-immersed lymphocyte (TIL) or NK cell therapy have positive results in clinical Phase I or Phase II trials for solid tumors, while other cell therapies such as cytokine-induced killer cells (an in vitro-induced NKT cell type) have positive results in clinical Phase III or Phase IV trials Compared with solid tumor adaptation, the new T-cell technology based on allogeneic transplantation has achieved more positive results in the early trials of hematoma Figure 5 Clinical trial results for cancer cell therapy (Photo: Nature Reviews Drug Discovery) Global development of the United States and China dominate the cancer cell therapy pipeline, and the number of research therapies in China is approaching the United States (508 vs 600) Most cell therapies in the United States are developed by pharmaceutical companies Although cell therapy in China has traditionally been developed by academic institutions, the number of cell therapies developed by pharmaceutical companies in China has outstripped those developed by academic institutions in the past year the number of preclinical cell therapies in China has almost tripled in a year, from 69 to 202 (Figure 6) The number of clinical stage I and Stage II cancer cell therapy in China increased by nearly 50% year-on-year, similar to the growth rate in the United States The U.S and China remain the leading in the number of clinical trials (871 in China; 718 in the U.S.) Figure 6 A clinical comparison of the new cancer cell therapy pipeline spent 2018-2020 (source: CRI IO Analytics and GlobalData) Summary and Outlook the number of cancer cell therapies in pre-clinical and clinical development is increasing, and the search for the same avariety therapy to a wider range of patients is increasing The new treatment is expected to be successful, but it remains to be seen whether the effectiveness of the same therapy is comparable, especially after the only approved allogeneic non-vaccine cell therapy was withdrawn from the EU market due to a lack of efficacy in stage III clinical phase III To date, most allion therapies are in the preclinical and early clinical development stages, and it may take some time for these therapies to gain extensive clinical validation Clinical trials of blood cancer and solid tumors using allogeneic cell therapy and somatic cell therapy have shown positive results, but these data are still limited and are mainly due to early trials that investigate product safety In addition, it is important to note that test data on negative results may not be publicly disclosed, which may lead to the appearance of positive results for most trials References: 1?Cancer Cell Therapies: The clinical trial landscape (Source: Nature Reviews Drug Discovery) Li Yuan Source: Medical Rubik's Cube Pro