Chimeric antigen receptor technology has proven successful in treating many types of liquid tumors, but its success has been limited in the treatment of solid tumor types. This is in part due to the microenvironment surrounding such tumors. The tumor stroma cells that comprise the tumor microenvironment produce this favorable environment through a variety of mechanisms, including by promoting therapy resistance through formation of a physical barrier between the tumor and tumor targeted therapies, promoting tumor growth through production of growth factors, chemokines and matrix proteins, by exerting an immunosuppressive influence through secretion of factors that attract immunosuppressive cells, regulate T-cell functions, modulate the phenotype of myeloid cells and by expressing inhibitory surface molecules. Therefore, targeting the tumor stroma cells that comprise this microenvironment is an attractive therapeutic approach. Importantly, these cells are non-cancerous and therefore genetically stable and less capable of developing resistance to potential therapeutic agents.
Stage of Development
Dr. Puré and colleagues have developed a chimeric antigen receptor (CAR) therapy specific for fibroblast activated protein (FAP). Adoptively transferred FAP-CAR T-cells selectively reduced FAP expressing stromal cells and inhibit tumors established by subcutaneous injection of mesothelioma (AE17.ova), lung cancer (LLC, LKR and TC1), colon carcinoma (CT26) cells into syngeneic mice, pancreatic (4662) cells in syngeneic as well as in immune incompetent NSG mice, and the growth of spontaneous pancreatic tumors in KPC mice.
Off-tumor toxicity resulting from FAP-CAR T cell administration was minimal. No abnormalities were observed in necropsy studies of visceral organs, skeletal muscle or bone marrow, and no anemia or weight loss occurred.
Issued and pending US and foreign patents cover compositions and methods of use.
This technology is available for licensing.
Wang et al. Cancer Immunol. Res. 2014; 2(2): 154-66. PMID: 24778279
Lo, A. et al. Cancer Research. 2015; 75(14):2800-2810. PMID: 25979873