Cancer Cell overview article interpretation! How to develop a new generation of cancer therapy for CAR-T cell engineering modification?

19, 2020 // -- In a review published in the international journal Lancer Cell entitled "Engineering CAR-T Cells for Next-Generation Cancer Therapy," scientists from the University of California and others discussed how CAR-T cells could be engineered for use as a new generation of cancer therapy.
Engineered T-cells that express tumor-specific chilayer antigens (CARs) have achieved remarkable results in treating patients with malignant blood tumors, and have revolutionized the field of step cell therapy, but achieving a broader therapeutic application of CAR-T cells requires a multi-layered engineering approach Improving the efficacy and safety of treatment, especially since the biological complexity of the tumor microenvironment (TME) often presents unique challenges to its treatment, the researchers discuss the latest strategies for improving CAR-T cell therapy by engineering the interactions between CAR proteins, T cells, T cells, and other components in TME.
photo source: Mihe Hong, et al. Cancer Cell (2020) doi:10.1016/j.ccell.2020.07.005 Inlay antigen receptor (CARs, chimeric antigen receptors) is a synthetic receptor that promotes T cells to identify tumor-related antigens (TAAs) in a way that is dependent on a major tissue compatible complex (MHC).
CAR-T cells targeted at pan-B cell marker CD19 showed unprecedented response rates in treating refractic B-cell malignancies, and became the first genetically modified cell therapy approved by the FDA; Effective CAR-T cell therapy for malignant tumors also requires more complex engineering tools to overcome the defensive mechanisms of tumors, such as immunosuppression, antigen escape, and physical barriers into solid tumors;
article, the researchers discussed: 1) the evolutionary history of CAR design, 2) the combination of antigen activation for logic gate-activated T cell activation, 3) the controllability and safety of on/off switches, 4) the safety control of adapter-dependent CARs; 5) the safety control of CAR-T cell activity; and 6) regulating the expression of CAR to improve CAR-T cells Safety; 7) site-specific CAR GMO insertion and allogeneic compatibility engineering modification; 8) promotes the expression of T-cell function; 9) self-secretion stimulation of CAR-T cells in tumor micro-environment; 10) tumor's home and penetration; 11) immunosuppressive axis destruction; 12) remodel tumor micro-environment to promote endogenetic immune response.
CAR-T cell therapy has great potential in treating malignant hematosoma disease, but scientists still face great challenges in treating solid tumors, so they need to further engineer and adjust the base to successfully treat these incurable malignancies, and recent protein and cell engineering strategies have made great progress in enhancing the internal adaptability and anti-tumor function of T cells. Tumor-specificity and inhibit tumor escape and recurrence, while enhancing immunotherapy solutions by modifying tumor micro-environments, and while most engineering strategies to date have focused on providing ideal individual characteristics, genome editing methods and genetic circuit design offer multiple levels of possibilities that promise to address the many problems and needs faced in the development of T-cell therapy.
At the same time, as advancing the clinical transformation of CAR-T cell therapy for solid tumors, researchers must carefully balance the biological complexity of T-cells, engineered and endoenvironomic immune cells, tumor cells, and other tumor-related factors with the potential crosstalk characteristics of different engineered characteristics.
With next-generation sequencing methods, single-cell sequencing techniques, and reduced and increased capacity for proteomics and metabolomic analysis, scientists may be able to understand and manipulate these complex interactions, while also helping scientists engineer next-generation CAR-T cell therapies. Retouched for solid tumor therapy, the growing T-cell engineering strategy toolbox collaborates and enables modular calibration for maximum safety and effectiveness, and continues to drive scientists to innovate to develop more new therapeutic strategies for difficult-to-treat diseases.
() References: Mihe Hong, Justin D. Clubb, Yvonne Y. Chen. Engineering CAR-T Cells for Next-Generation Cancer Therapy, Cancer Cell (2020) doi:10.1016/j.ccell.2020.07.005