Incorporating co-stimulatory signaling in CAR T Cells

This podcast delves into the exciting world of cancer immunotherapy, focusing on the evolution of cancer vaccines and the recent surge of cell-based therapies. This series follows a string of primary research papers highlighting the most impactful advances in CAR T Cell therapy. It is a companion to a KU Edwards Campus Biotechnology course, but it contains information interesting to anyone who wants to understand the mechanics of this therapy. It begins with a 1998 Journal of Experimental Medicine article by Krause et al. that details the creation of a chimeric receptor, 3G6-CD28, that incorporates the signaling domain of CD28 in the cytoplasmic portion of the antigen receptor to enhance the survival and proliferation of T lymphocytes targeting tumor cells. Experiments using Jurkat cells and human primary T cells demonstrate that the 3G6-CD28 chimeric receptor triggers CD28 signaling upon GD2 recognition, improving T cell survival and expansion, especially in the presence of anti-CD3 stimulation. This approach offers a potential strategy for improving cell-based immunotherapy by overcoming the limitations of tumor cells' poor antigen presentation and lack of costimulatory molecules. The results show a significant improvement in T-cell activity against tumor cells.