Immunotherapies, which unleash the immune system on cancers, have revolutionized cancer treatment but have so far had limited efficacy against the deadly brain cancer glioblastoma.
Many immunotherapies spur T cells to go after tumors by blocking checkpoint proteins that normally restrain the immune cells. To look for immunotherapy targets that might help treat glioblastoma, Sidi Chen, PhD, associate professor of genetics, used the gene-editing technique CRISPR to knock out genes encoding various cell-surface and membrane proteins in mouse T cells, then injected these CRISPR-edited T cells into mice with glioblastomas.
As reported in Nature Biotechnology, Chen and colleagues found that mice injected with T cells from which the gene Pdia3 had been knocked out using CRISPR gene editing survived longer than those injected with T cells that were not edited. Further, according to experiments done in cell culture, chimeric antigen receptor (CAR)-T cells engineered to attack glioblastoma were more effective if Pdia3 was knocked out.
The results, says study co-author and Chen lab postdoc Lupeng Ye, PhD, suggest that targeting Pdia3 in CAR-T cells could make them better killers of glioblastoma.