Development of Anti-Cadherin-17 Antibody - IR700 Conjugate for Photodynamic Therapy Against Gastrointestinal Cancers
Refereed conference paper presented and published in conference proceedings


摘要The lack of tumor specificity by photosensitizers often hampers clinical application of photodynamic therapy (PDT). Delivery of photosensitizer to tumor based on enhanced permeability and retention effect could lead to non-specific 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), a water-soluble photosensitizer with excitation wavelength 689nm, can produce reactive oxygen species (ROS) efficiently upon light irradiation. Previous studies have found that IR700 antibody conjugate could produce potent phototoxicity. By conjugating IR700 to anti-Cadherin-17 (CDH17) humanized monoclonal antibody (ARB102), the conjugate will be able to target CDH17+ cancer cells and achieve selective accumulation to induce potent cytotoxicity upon light irradiation. CDH17 is a cell surface antigen commonly overexpressed in gastrointestinal cancers. Normal tissue expression of CDH17 is limited to small intestine and colon, which are shielded from external light exposure. The capability of ARB102-IR700 conjugate to target tumor and light-activatable ROS production will limit off-target adverse effect. In vitro studies of ARB102-IR700 PDT has found that it can cause light-induced cytotoxicity in CDH17+ cancer cells at high potency and specificity. In a co-culture system of CDH17+ and CDH17- cells, ARB102-IR700 PDT can achieve targeted killing of CDH17+ cancer cells while leaving the CDH17- cells unharmed. The underlying cell death mechanism and pathway will be investigated. In vivo targeted PDT killing of CDH17+ cancer cells using the ARB102-IR700 conjugate will also be studied as well.
著者LUM Yick Liang, NG Kee Pui Dennis, LUK M John, FONG Wing Ping
會議名稱17th International Photodynamic Association World Congress
會議地點Cambridge, Boston, MA
會議論文集題名Proceedings of SPIE
關鍵詞cadherin-17, gastrointestinal cancers, immunoconjugate, IRDye 700DX, photodynamic therapy, photoimmunotherapy

上次更新時間 2021-18-10 於 00:53