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[SCItalk] Alba Rodriguez-Garcia: Developing CAR-T cell therapies for ovarian cancer: Targeting tumor cells and macrophages in the tumor microenvironment

Alba Rodriguez-Garcia
University of Pennsylvania, PA, USA

 

 

Chimeric antigen receptor (CAR) T-cell therapy for solid tumors has not yet recapitulated the unprecedented clinical responses achieved by targeting CD19 in hematologic malignancies. In fact, complete responses have been anecdotal in solid tumors. The lack of good target antigens, such us CD19, that are homogenously, selectively, and highly expressed in tumor cells remains a challenge in the field. Here, we will discuss the development and evaluation of CAR T-cells targeting a novel tumor antigen, MISIIR, which is overexpressed in the majority of gynecologic cancers. T-cells expressing a MISIIR-specific CAR demonstrated antigen-specific reactivity in vitro and eliminated MISIIR-overexpressing tumors in vivo. MISIIR CAR T-cells also recognized a panel of human ovarian and endometrial cancer cell lines, and lysed patient-derived tumor specimens in vitro, without mediating cytotoxicity of a panel of normal primary human cells.

Another main hurdle encountered for the application of CAR T-cell therapy to solid tumors is the presence of a hostile immunosuppressive tumor microenvironment (TME). We will also discuss the development of CAR T-cells engineered to target tumor associated macrophages (TAMs) in the tumor microenvironment, instead of directly targeting the tumor cells. We have demonstrated that the immunosuppressive population of TAMs can be specifically depleted by using CAR T-cell therapy in a syngeneic mouse model of ovarian cancer, resulting in TME reprogramming and control of tumor progression.

 

 

Dr. Alba Rodriguez-Garcia received her PhD in Biomedicine from the University of Barcelona in 2015. Her doctoral studies were conducted in the laboratory of Dr. Ramon Alemany at the Institute of Biomedical Research of Bellvitge (IDIBELL), focusing on the development of novel anticancer therapies in the area of oncolytic adenoviruses. She is currently a postdoctoral fellow in the laboratory of Dr. Daniel Powell Jr. at the Ovarian Cancer Research Center (OCRC) and the Center for Cellular Immunotherapies (CCI) at the University of Pennsylvania (UPENN), PA, USA. Since then, her research has focused on developing CAR T-cell therapies for ovarian cancer, exploring novel tumor-specific antigen targets and strategies to reprogram the immunosuppressive tumor microenvironment, which limits activity of tumor-specific T-cells in solid tumors. During her postdoc training, Dr. Rodriguez-Garcia has been awarded the Stand Up to Cancer Ovarian Cancer Dream Team Grant by the Sandy Rollman Ovarian Cancer Foundation (SROCF), and the Ann and Sol Schreiber Mentored Investigator Award by the Ovarian Cancer Research Alliance (OCRA).