Engrafting human regulatory T cells with a flexible modular chimeric antigen receptor technology.

Engrafting human regulatory T cells with a flexible modular chimeric antigen receptor technology. J Autoimmun. 2018 Mar 01;: Authors: Koristka S, Kegler A, Bergmann R, Arndt C, Feldmann A, Albert S, Cartellieri M, Ehninger A, Ehninger G, Middeke JM, Bornhäuser M, Schmitz M, Pietzsch J, Akgün K, Ziemssen T, Steinbach J, Bachmann MP Abstract As regulatory T cells (Tregs) play a fundamental role in immune homeostasis their adoptive transfer emerged as a promising treatment strategy for inflammation-related diseases. Preclinical animal models underline the superiority of antigen-specific Tregs compared to polyclonal cells. Here, we applied a modular chimeric antigen receptor (CAR) technology called UniCAR for generation of antigen-specific human Tregs. In contrast to conventional CARs, UniCAR-endowed Tregs are indirectly linked to their target cells via a separate targeting module (TM). Thus, transduced Tregs can be applied universally as their antigen-specificity is easily adjusted by TM exchange. Activation of UniCAR-engrafted Tregs occurred in strict dependence on the TM, facilitating a precise control over Treg activity. In order to augment efficacy and safety, different intracellular signaling domains were tested. Both 4-1BB (CD137) and CD28 costimulation induced strong suppressive function of genetically modified Tregs. However, in light of safety issues, UniCARs comprising a CD137-CD3ζ signaling domain emerged as constructs of ...
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research