Research Projects

Objective 1: Culturing and Engineering T Cells for Sarcoma Specificity 

Cancer-testis antigens are proteins that are normally restricted to male germ cells in adults, but often re-expressed in many cancer types. As they are not seen in normal adult tissues, other than testis, these are attractive immunotherapy targets. Although many cancers express these proteins, synovial sarcoma and myxoid/ round cell liposarcoma express them more strongly and consistently than other cancers. NY-ESO-1 is one of the best-known members of this group of proteins. Dr. Pollack’s team developed a method to isolate and expand NY-ESO-1–specific T cells from the peripheral blood of sarcoma patients and tested them in a clinical trial that showed clinical activity. Based on this work, the Pollack lab is developing ways to make sarcoma-targeting T cells with even greater specificity and improved function.

The Pollack Lab is also applying techniques they developed for their adoptive T cell therapy trials to study immune responses, using blood samples from sarcoma patients treated on trials of novel immunotherapies. One notable trial is using a lentiviral NY-ESO-1 vaccine (sponsored by Immune Design). Early data suggest this vaccine can increase NY-ESO-1 specific immune responses in patients and has the potential for impressive clinical antitumor activity. 

Clinical grade NY-ESO-1 specific cell generation for a SS patient
Clinical grade NY-ESO-1 specific cell generation for a SS patient From: Pollack et al. Journal of Immunotherapy of Cancer, 2014.

Objective 2: Overcoming the Sarcoma Tumor Immune Microenvironment

The Pollack team is expert in processing successive small tumor biopsies for state-of-the-art immune monitoring. In recent studies, Dr. Pollack learned that tumors can grow despite persistence of functional anti-tumor T cells and persistent expression of target antigen. This led to a project dissecting the tumor immune microenvironment of the most common sarcoma subtypes. The Pollack team found that microenvironments in certain subtypes, such as undifferentiated pleomorphic sarcoma, are very inflammatory (with lots of T cells); other subtypes, including synovial sarcoma and myxoid/round cell liposarcoma, are immunologically quiet. They started focusing on manipulating the tumor immune microenvironment to enhance antitumor responses, and developing techniques to characterize in detail changes in the sarcoma microenvironment following therapy, using samples from patients enrolled on our trials.

Increased inflammatory gene expression in undifferentiated pleomorphic sarcoma (UPS)
Increased inflammatory gene expression in undifferentiated pleomorphic sarcoma (UPS) From: Pollack et al. Cancer, 2017. High-res version