From insulin to lowering environmental strain to grow food, genetic engineering is one of the marvels of the 20th century. In the 21st, CRISPR-Cas9 or something else may achieve the same lofty status but genetic engineering isn't done yet.

Glioblastoma is an aggressive cancer in the brain or spinal cord, with a very short life expectancy. The usual treatment is temozolomide chemotherapy (TMZ) to slow or stop the growth of the cancer cells and the United States Food and Drug Administration clearance of an Investigational New Drug, application to launch a Phase 2 clinical trial. The trial will target newly diagnosed glioblastoma, using IN8bio’s proprietary drug-resistant immunotherapy and assess safety, efficacy and tolerability of genetically modified DeltEx drug-resistant immunotherapy, or DRI, cells at leading medical centers across the United States.

The DRI technology uses gamma-delta T cells, and it is licensed from the UAB Research Foundation and two other institutions. Gamma-delta T cells are a specialized population of T cells that possess unique properties, including the ability to differentiate between healthy and diseased tissue.

When tumors are damaged by TMZ treatment, they develop stress-induced ligands on the cell surface. Normally, these signals would incite the immune watchdog gamma-delta T cells to recognize and kill the damaged tumor cells. TMZ therapy kills lymphatic immune cells, including the gamma-delta T cells. This hinders the immune system’s ability to leverage the TMZ-induced state of increased tumor vulnerability.

In DRI, gamma-delta T cells are purified from peripheral blood mononuclear cells, and then given a gene that makes them resistant to TMZ. Next, the drug-resistant gamma-delta T cells are expanded and given to a patient, concomitantly with TMZ chemotherapy. The resistant gamma-delta T cells should then be able to recognize the stress-induced ligands on the surface of TMZ-treated tumor cells and start to eliminate them.