In the fight against cancer, chimeric antigen receptor T cell (CAR-T) therapy has achieved notable success in treating blood cancers. However, it has been largely ineffective against solid tumors. Now, a newly published study by UNC Lineberger Comprehensive Cancer Center researchers demonstrates that a different immunotherapy approach utilizing natural killer T (NKT) cells produced significant antitumor activity in preclinical models of solid tumors.
Gianpietro Dotti, MD, professor of microbiology and immunology at UNC School of Medicine and co-leader of the UNC Lineberger immunology research program, Xin Zhou, PhD, a postdoctoral fellow in the Dotti lab, and their colleagues report that CAR-natural killer T cells (CAR-NKT) utilize a multimodal approach, combining direct tumor cell killing, reprogramming of the tumor microenvironment, and promotion of systemic immune responses, to create a more immunogenic environment in tumors. Their findings are published in Nature Cancer . CAR-T cells are very potent cells.
However, the most surprising finding in our work is that these potent cells are strongly inhibited in tumor models that recapitulate the complexity of the tumor microenvironment. In particular, tumor-associated macrophages seem to have a potent inhibitory effect on CAR-T cells. CAR-NKT seem capable to avoid the inhibitory effects of macrophages since they can directly target them.
" Gianpietro Dotti, MD, professor of microbiology and immunology at UNC School of Medicine,.