Development of anti-cadherin-17 antibody -IR700 conjugate for photodynamic therapy against gastrointestinal cancers

Abstract

The lack of tumor specificity by photosensitizers often hampers the clinical application of photodynamic therapy (PDT). Delivery of photosensitizer to tumor based entirely on the enhanced permeability and retention effect could lead to nonspecific uptake of photosensitizer by normal tissue, causing adverse effect in patients. Accumulating evidence showed that the combination of antibody immunotherapy and PDT can complement each other to produce effective cancer-targeted photoimmunotherapy. IRDye 700DX (IR700) is a water-soluble phthalocyanine-based photosensitizer that can produce reactive oxygen species (ROS) efficiently upon light irradiation. Cadherin-17 (CDH17) is a cell surface antigen commonly overexpressed in gastrointestinal cancers. By conjugating IR700 to anti-CDH17 humanized monoclonal antibody (ARB102), the conjugate could target CDH17 positive cancer cells and achieve selective accumulation to induce potent cytotoxicity upon light irradiation.