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45-1 Ramsey Road, Shirley, NY 11967, USA
USA: 1-631-871-5806
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Smarter™ Safety CAR Construction Service

T cell therapies have shown remarkable clinical efficacy in bone marrow and organ transplantation, cancer immunotherapy, viral infections, and auto-immune diseases. However, T cell are also involved in deleterious side effects. For instance, administration of engineered T cells can damage the normal tissues due to on-target/off-tumor effects. Physiological regulation of T cell activation is achieved by several mechanisms including immune inhibitory receptors such as CTLA4 and PD1, which play pivotal roles in reducing or terminating T cell responses. Inhibitory receptors can be up-regulated during T cell priming to taper immune responses or basally expressed to regulate activation thresholds. A safety CAR (sCAR) contains an extracellular scFv fused to inhibitory domains that prevent the activity of CAR-T cells.

For example, mice deficient of the inhibitory domain CTLA-4 exhibit massive T cell activation and proliferation and eventually succumb to severe systemic autoimmune disease with infiltration of activated T cells. Moreover, loss of PD-1, another inhibitory signaling domain specifically expressed on activated T cells, induces progressive arthritis and accelerates insulitis in nonobese diabetic (NOD) mice. Thus, modulation of the inhibitory signaling domain CTLA-4 or PD-1 during T cell stimulation can selectively divert off-target immunotherapy responses.

Safety chimeric antigen receptor models and concepts

Safety chimeric antigen receptor models and concepts
Nature Reviews Cancer. 2016.

Creative Biolabs possesses the most exquisite service platform for CAR-T cell therapy. With efforts from numerous researches and years of experience, we have developed a variety of effective methods to improve the safety for CAR-T cell therapy. Safety CAR can regulate the activity of T cells, and inhibit the secretion of cytokine and off-tumor effect, further improve the safety of CAR-T cell therapy. Creative Biolabs provides the most advanced safety CAR construction service for customers all over the world.

References

  1. Fesnak, et al. "Engineered T cells: the promise and challenges of cancer immunotherapy." Nature Reviews Cancer 16.9 (2016): 566-581.
  2. Fedorov, et al. "PD-1–and CTLA-4–based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses." Science translational medicine 5.215 (2013): 215ra172-215ra172.

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CONTACT US

USA
45-1 Ramsey Road, Shirley, NY 11967, USA
Tel: 1-631-871-5806
Fax: 1-631-207-8356
Email:

Europe
Ringstrasse 4, 64401 Gross-Bieberau, Germany
Tel: 44-207-097-1828

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