Researchers engineer a herpes virus to turn on T cells for immunotherapy

Recent research points to the potential utility of a familiar sounding foe–herpes virus–in the fight against cancer.

The idea: the virus has evolved to commandeer cellular machinery in order activate signaling pathways inside cells and these strategies can be repurposed to bolster immunotherapy against diseases like cancer.

T cells are front line defenders against pathogens, like viruses, and cancer because they can kill infected or malignant cells.

Scientists have for years been trying different techniques to direct these immune cells to protect against disease.

CAR-T therapy is one such example of prompting the body’s own immune system to attack certain forms of cancer using T cells. 

However, the therapeutic potential of T cells can be limited by the suppressive environment present within tumors that impairs T cell survival and function.

The University of Michigan team identified herpes virus saimiri, which infects the T cells of squirrel monkeys, as a source of proteins that activate pathways in T cells that are needed to promote T cell survival.

The work, led by the lab of Adam Courtney, Ph.D., in the Department of Pharmacology and the U-M Rogel Cancer Center, exploits this ability in order to investigate whether a modified viral protein could be used to activate transcription factors known as STAT proteins.

The approach is borne of observations that stimulation of the JAK-STAT5 pathway by cytokines like interleukin-2 (IL-2) helps boost the therapeutic ability of T cells to kill cancer cells.

The team engineered a variant of the tyrosine kinase interacting protein from the herpes virus to bind LCK (a kinase active in resting T cells) and recruit it to activate STAT5.

In this way, the team determined that direct activation of STAT5 could sustain T cell function in tumors of mouse models of melanoma and lymphoma.

Their findings hint at a new approach—using genes from organisms with proven ability to modulate human cells—to enhance the power of immunotherapy.

Ph.D. candidate Yating Zheng, of the Department of Pharmacology at U-M Medical School is first author of the paper.

Additional authors: Zehui Gu, Claire E. Shudde, Taylor L. Piper, Xinyu Wang, Grace A. Aleck, Jiajia Zhou, Dana King, Monica K. Chanda, Lilliana Trinch, and Weiping Zou

Paper cited: “An engineered viral protein activates STAT5 to prevent T cell suppression,” Science Immunology. DOI: 10.1126/sciimmunol.adn9633