A yeast-based approach to the development of antibodies targeting cancer-associated fibroblasts

摘要

An expanding body of work suggests that the tumor stroma plays an integral role in the initiation and development of epithelial cancers. Within the stroma, cancer-associated fibroblasts (CAFs) are involved in several functions that form key aspects of tumor progression, including immune suppression, metabolism, and invasion and metastasis. Despite the demonstrated importance of CAFs within the tumor microenvironment, targeting CAFs in a therapeutic context remains a challenge. The work presented here details the development of a suite of antibodies targeting multiple epitopes of fibroblast activation protein (FAP), a membrane-bound protease selectively overexpressed on CAFs in numerous epithelial cancers. More than 50 unique antibodies were identified in initial yeast-based screening efforts. Subsequent characterizations enabled the isolation of a subset of antibodies recognizing both the human and murine forms of the antigen and the identification of antibodies with a range of functional properties. These antibodies are currently being used to examine the effects of targeting CAFs in mouse models of cancer.