Bob McGray, PhD
2023 Early Career Investigator Grant Recipient
Roswell Park Cancer Institute
BiTE-secreting T cells for Adoptive T cell Therapy in Ovarian Cancer
Project Summary
Cancer immunotherapies use the body’s own immune system to fight cancer. While immunotherapies can be very effective for certain cancers ovarian cancer (OC) patients often do not benefit from these treatments, suggesting a clear need for new therapeutic options. T cells (a type of immune cell) have emerged as key drivers of tumor destruction after immunotherapy and OC patients with higher numbers of T cells in their tumors have improved survival. Our goal is to develop a novel T cell-based OC treatment, where T cells are modified to secrete a protein that programs T cells to recognize and attack tumors. After the modified T cells are injected, the secreted protein (called a BiTE), produced by BiTE-T cells, causes the injected BiTE-T cells to attack the tumor and also instructs T cells already present in the tumor to attack the cancer. This “Tag Team” approach to T cell therapy increases tumor destruction and has the potential to completely eliminate tumors, leading to long-term cures. In this proposal, we will use mouse OC models and OC patient specimens to identify approaches that maximize the benefit of BiTE-T cells in OC. This includes testing universal (off the shelf) BiTE-T cells, which can be prepared in large numbers and be readily available for treatment, thereby increasing the number of OC patients that benefit from this therapy. Findings from these studies will provide important information to help us develop this new immunotherapy to effectively treat OC patients.
Bio
I completed my PhD training at McMaster University in the laboratory of Dr. Jonathan Bramson prior to coming to Roswell Park Comprehensive Cancer Center as a Postdoctoral Fellow. While a Postdoc at Roswell Park, I trained in the laboratory of Dr. Kunle Odunsi, a world leader in developing immunotherapies for ovarian cancer. Working with Dr. Odunsi, I focused on approaches to effectively combine oncolytic virotherapy with cancer vaccines, adoptive T cell transfer (ACT), and checkpoint inhibitors to enhance antitumor immunity in the context of advanced and metastatic cancer. While a Postdoc, I was awarded the OCRA Ann and Sol Schreiber Mentored Investigator Award (Mentor: Dr. Kunle Odunsi), where my studies focused on combining oncolytic virotherapy with ACT. Following my Postdoctoral training, I spent two years working at a clinical stage Biotech company (Northern Biologics) developing cancer immunotherapies prior to returning to Roswell Park to start my own laboratory. Since starting my own lab, I have focused on utilizing immune cell engagers (e.g. BiTEs/TriTEs/Innate Cell engagers; ICEs) to direct T cells or other immune cells to target both the tumor and surrounding stroma. Specifically, we are exploring strategies of improving both local immune cell engager activity and duration of effective delivery in the tumor microenvironment through engineering engager ‘armed’ immune cells for adoptive cell transfer.