Immune Stimulating Antibody ‐Photosensitizer Conjugates via Fc‐Mediated Dendritic Cell Phagocytosis and Phototriggered Immunogenic Cell Death for KRAS‐Mutated Pancreatic Cancer Treatment

Antibody ‐photosensitizer conjugates that specifically bind to epidermal growth factor receptor overexpressing tumor are designed for both innate and adaptive immune response, resulting in synergism of antitumor effect. The conjugates provoke immunogenic cell death via photodynamic therapy and facilitate a ntigen phagocytosis as well as maturation effect of dendritic cells. Finally, antibody‐photosensitizer conjugates eliminate the solid tumor and offer long‐term anticancer immunity. AbstractAlthough cetuximab (CTX) is a chimeric epidermal growth factor receptor (EGFR) antibody, the antitumor efficacy of CTX has a negligible effect in patients withKirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutated pancreatic adenocarcinoma. Given that all extant treatments are ineffective due to the undruggable characteristics ofKRAS‐mutated cancer, alternative strategies have been investigated. In this work, CTX‐conjugated maleimide‐polyethylene glycol‐chlorin e6 (CMPC) is designed to strengthen its antitumor efficacy. With strong affinity for EGFR overexpressing Aspc‐1 cells, CMPC with laser exerts the greatest cyto toxicity (90%) and induction of immunogenic cell death. Through a combination of fragment crystallizable region‐mediated antigen uptake by CTX and danger‐associated molecular patterns released by photodynamic therapy (PDT), phagocytosis and maturation of dendritic cells treated with CMPC plus la ser show dramatic increases. In vivo biodistribution an...
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research