Einstein researchers awarded $2.6 million NIH grant to develop effective cancer immunotherapies

The National Institutes of Health has awarded two co-investigators at Albert Einstein College of Medicine a five-year, $2.6 million grant to make immunotherapy agents that more precisely and effectively treat a variety of cancers while causing far fewer side effects than current immunotherapies.

The two investigators are Steven C. Almo, Ph.D., professor and chair of biochemistry, professor of physiology & biophysics and Wollowick Family Foundation Chair in Multiple Sclerosis and Immunology at Einstein; and Chandan Guha, M.B.B.S., Ph.D., professor in the departments of radiation oncology, of pathology and of urology at Einstein and vice chair of radiation oncology at Einstein and Montefiore Einstein Center for Cancer Care.

Immunotherapy has emerged as a highly promising strategy against cancer. It involves manipulating T cells, a type of white blood cell that helps destroy invaders such as viruses and bacteria and that can potentially eliminate cancer cells as well. But existing immunotherapies have significant drawbacks. They focus on a small number of therapeutic targets and work against only a few types of cancer; and because they stimulate or inhibit all T cells, rather than a select few, current immunotherapies often cause harmful side effects that can be fatal.

The Einstein researchers have developed a novel immunotherapy strategy for directing T cells to attack specific types of cancer while also modulating their behavior: The researchers can rev up T-cell activity to attack cancer cells or suppress their activity in situations where immunotherapy is aimed at treating autoimmune diseases. The strategy involves modulating T cells with a single "fusion protein" containing two parts: (1) a protein that acts like a "zip code" to specifically target only those T cells relevant to a particular type of cancer or disease; and (2) a molecule tailored to either activate or inhibit the precisely targeted T cells by stimulating particular receptors on their surfaces.

The researchers refer to their synthetic protein as a synTac, for "artificial immunological synapse for T-cell activation."

The Einstein researchers have already developed a number of different synTacs that have worked both in cells and in mice. The NIH grant will allow them to develop additional synTac fusion proteins and to evaluate their efficacy in mouse models of melanoma and pancreatic cancer. They expect that their synTacs will trigger an increase in the number of melanoma-specific and pancreatic-specific T cells, causing tumors in both mouse models to regress significantly. The long-term goal is to create new and more effective immunotherapies and ultimately translate these strategies to the clinic.