Role of CD28 costimulation in T cell receptor gene therapy of cancer
Final Report Abstract
Conclusions. CD58 is an universal target for clinical delivery of CD28 costimulation because is broadly expressed on different cancers. Expression of CD58 on target cells is important for optimal T cell-target cell recognition. Costimulation through chimeric CD2-CD28 coreceptor enhances TCR gene-modified effector function, survival and proliferation in vitro, and has a beneficial effect on T cell function in vivo. The beneficial effect was also present with low Ag/CD58 expression on target cells. Despite the deviations from the initial experimental plan, the developed project has managed to answer the main questions asked in the original grant proposal and covered both of the milestones. I have demonstrated that CD28 plays an important role in TCR modified-T cell function, and that this beneficial effect could be extrapolated for clinical application by using CD2-CD28 costimulatory receptors. With CD58 as universal target, this new therapeutic approach has the potential for broad clinical impact.
Publications
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(2021). “CD28 costimulus achieves superior CAR-T cell effector function against solid tumors than 4-1BB co-stimulus”. Cancers 13(5): 1050
Textor A, Grunewald L, Anders K, Klaus A, Schwiebert S, Winkler A, Stecklum M, Rolff J, Henssen AG, Hopken UE, Eggert A, Schulte JH, Jensen MC, Blankenstein T, Kunkele A
