Transgenic T cells with enhanced anti-tumor cytotoxicity to treat cancers

­CAR T cell therapy recently achieved success in treating blood cancers. Drugs Kymriah and Yescarta are FDA approved for treating hematological malignancies. However, existing T cell therapies are not effective in treating solid tumors, partly due to T cell exhaustion and lack of sufficient memory T cell populations.

GW researchers invented a way to engineer T cells that exert anti-tumor cytotoxicity for a longer duration. Engineered T cells over expressing COBRA-1 protein, avoid T cell exhaustion and have larger memory T cell populations. This results in significantly higher tumor killing activity. The researchers demonstrated the advantages by treating tumor bearing mice with unmodified or COBRA-1 transgenic T cells.

Figure: Immunodeficient mice were given either wild-type (WT-Blue) or COBRA-1 transgenic (Tg-Red) CD8+ T cells, one day before subcutaneous transplantation of E0771 tumor cells. Tumor volumes were measured every 3-4 days, and the data indicated an enhanced reduction in tumor size with Tg T cells (Wu et al., Nature Communications 2022).

Applications: 

•  Enhance the efficacy of any T cell therapy (including CAR T) for any tumor type

Advantages: 

• Increase tumor cell killing
• Avoid T cell exhaustion
• Increase population of memory T cells

Publications:

Wu et al. RNA polymerase II pausing factor NELF in CD8 + T cells promotes antitumor immunity. Nature Communications 2022 (PMID: 35444206)