Smarter™ Self-destruct CAR Construction Service

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

CAR-T cells, re-directed to tumor-associated antigens (TAA), have shown promising results in clinical trials and some patients have even undergone complete tumor regression. However, current CAR-T cell therapy needs more careful balance between T-cell activation (ensure antitumor activity) and the potential of uncontrolled activation that may induce immunopathology. For example, rapid tumor cell clearance may induce cytokine release syndrome and tumor lysis syndrome, which are both dangerous complications during CAR-T therapy. On-target/off-tumor activation of CAR-T cells by low level expression of targets on non-malignant tissues has also been associated with many severe toxicity and even death in some cases. In order to control these adverse responses of T cell therapy, the Self-destruct CAR has been developed. Specifically, CAR-T cells are engineered to express self-destruct CAR through RNA electroporation or viral transduction. The self-destruct CAR plays as a molecular switch, which negatively controls the performance of T cell therapy through the elimination of CAR-T cells and further ensures the safety of T cell therapy. With a newly established platform to engineer T cells by RNA electroporation and viral transduction, Creative Biolabs provides the self-destruct CAR construction service for clients all over the world.

Self-destruct chimeric antigen receptor models and concepts

Self-destruct chimeric antigen receptor models and concepts
Nature Reviews Cancer. 2016.

The self-destruct CAR has exhibited potent antitumor effects and improved safety in preclinical xenograft models of human mesothelioma and advanced leukemia. The off switch suicide gene, herpes simplex virus thymidine kinase (HSV-TK), can be induced by ganciclovir and clear CAR-T cells after or during the gene therapy trials. Another suicide gene, inducible human caspase 9 (iCasp9), can also be induced by intravenous administration of FK506 binding protein (FK506BP) and remove CAR-T cells in animal experiments through apoptosis.

Creative Biolabs provides self-destruct CAR construction service for clients across the world. As a leading company in immunotherapy development, Creative Biolabs can provide various products and services related to CAR-T cell therapy. We provide services on the most advanced fourth generation CAR to work with our clients to develop more potent and safe CAR-T treatment methods.

References

Fesnak, et al. "Engineered T cells: the promise and challenges of cancer immunotherapy." Nature Reviews Cancer 16.9 (2016): 566-581.
Beatty, et al. "Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce antitumor activity in solid malignancies."Cancer immunology research 2.2 (2014): 112-120.
Gargett, et al. "The inducible caspase-9 suicide gene system as a "safety switch" to limit on-target, off-tumor toxicities of chimeric antigen receptor T cells." Frontiers in pharmacology 5 (2014): 235.
Jensen, et al. "Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans." Biology of Blood and Marrow Transplantation 16.9 (2010): 1245-1256.
Zhao, et al. "Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor." Cancer research 70.22 (2010): 9053-9061.