Immunotherapy has become the backbone of cancer treatment. Among them, chimeric antigen receptor (CAR) T cells have achieved great success in the treatment of hematological malignancies. However, CAR T treatment for solid tumors is less effective. Antigen targeting, CAR T cell infiltration, proliferation, and persistence are the main obstacles preventing CAR T treatment from spreading to solid tumors. To overcome these obstacles, the next generation of CAR T cells will need more effective anti-tumor properties, which can be achieved through gene-editing technology.
At Creative Biolabs, we always keep pace with the most cutting-edge progress and master innovative strategies to enhance CAR T cell function by improving target recognition, persistence, transportation, and overcoming inhibitory TME. Empowered by the advanced Smart™ CAR development platform, Creative Biolabs is capable of providing a variety of next-generation CAR vector products, such as synnotch CAR, universal CAR, overexpression CAR and switch CAR, etc. These next-generation CAR structures can improve antigen recognition capabilities and reduce immune escape.
By optimizing costimulatory signals and overexpressing cytokines, the proliferation and persistence of CAR T cells can be enhanced. CAR T cells equipped with chemokines or chemokine receptors help overcome their poor ability to home to the tumor site. Strategies such as eliminating immune checkpoint molecules and incorporating dominant negative receptors and chimeric switch receptors may contribute to the depletion or reversal of negative T cell regulatory factors in TME. Moreover, it has been proposed that to overcome the low and variable expression of tumor-specific antigens, multiple antigens could be targeted simultaneously using dual CAR-T cells that express two CARs on their surface, or use more novel CAR designs, such as tandem CAR-T cells, combined CAR or synNotch receptors.
In summary, the current new strategies for enhancing CAR T cell function and improving the therapeutic response to solid tumors mainly include: targeting multiple antigens, overexpressing cytokine or chemokine receptors, enhancing costimulatory signals, and eliminating negative T cells regulators. These next-generation CAR T cells have shown promise in preclinical models, and they have broad prospects in the treatment of solid tumors.
Creative Biolabs provides multiple novel non-regular CARs, including but not limited to:
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