CAT-BLAST: Engineered bacteria for robust targeting and elimination of cancer-associated fibroblasts

Abstract

Cancer-associated fibroblasts (CAFs) construct a protective stromal barrier that promotes tumor growth and resistance to therapy. To dismantle this, we developed CAT-BLAST, an engineered bacterial platform designed to potently eliminate these cells. We engineered a safe, high-expression E. coli chassis, arming it with a FAP-specific synthetic adhesin for precise CAF targeting and the ability to secrete the ClyA cytotoxin to induce apoptosis in both CAFs and adjacent tumor cells. This platform demonstrated robust, FAP-specific targeting across diverse human tumor xenograft models and achieved significant tumor suppression in both murine colorectal cancer and melanoma.