Compare to CAR-T cells generated with traditional CARs, Armored CAR-T cells express immune checkpoint receptors that are able to regulate immune checkpoint signaling. High expression of immune checkpoint ligand is an efficient way for tumor cells to escape immune surveillance. This immune escape mechanism is also a major way for tumor cells to avoid adoptive T cell therapy. The tumor microenvironment contributes significantly to tumor development by inhibiting immune responses.
Armored chimeric antigen receptor models and concepts
Nature Reviews Cancer. 2016
CAR-T cell therapy has become a central approach in cancer treatment. The success of CAR-T cell treatment requires them to survive and expand in vivo. However, most tumors employ an immune evasion mechanism to escape the infused CAR-T cells, which results in the production of many inhibitory cytokines that prevent T-cell persistence and effector functions. Various methods, such as regulating the cell-cell signaling, administration of cytokines and infusion of new generation CAR-T cells, are used to tackle the immunosuppression effect of tumors. The Armored CAR-T cells that express an immune checkpoint switch receptor have an improved efficacy. For example, Armored CAR-T cells expressing dominant negative transforming growth factor-β type II receptor (DNRII) confer T cell resistance to tumor production. The T cells expressing hybrid receptors comprising exodomain IL-4 and endodomain IL-7 can be activated by IL-4, which is a tumour-generated suppressive cytokine. The programmed cell death protein 1 (PD1) monoclonal antibody has shown the ability to enhance the efficiency of CAR-T cells in preclinical models. These results indicate that both endogenous immune cells and engineered T cells are subject to tumor immune suppression by immune checkpoints. T cell therapy can incorporate different forms of immune checkpoint blockade to further enhance their efficacy.
As the leading biotech company that provides CAR-T cell therapy related services, Creative Biolabs has the most advanced technology and extensive experience and thus, is able to offer the best products and services. Here we present the SmarterTM Armored CAR construction service including the design and construction of CAR, virus packaging, T cell engineering and the in vitro and in vivo test of CAR-T cell therapy.
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