Abstract C016: New treatment modality for pancreatic cancer-Vascular Targeted Photodynamic therapy with WST11 (Padeliporfin) combined with endovascular light delivery

Abstract

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. Early detection and surgical removal of PDAC, when the cancer is localized with no clinical evidence for systemic spread, may be curative but tumor spread into the vicinity of major blood vessels, e.g. superior mesenteric artery (SMA), can be lethal and therefore avoid surgery. Here we show that Vascular Targeted Photodynamic therapy (VTP) with WST11 in combination with immune modulating chemotherapeutic agents allows PDAC tumors ablation while preserving large normal vessels and tissues in animal models. New endovascular illumination system recently developed by our group (1) provides the light needed for such ablation with no damage to the SMA and complete remodeling of the surrounding normal tissue. Methods: Two orthotopic models of pancreatic cancer (KPC-Luc-mcherry and non-labeled KPC tumors (NL-KPC)) in C57B mice were subjected to VTP, alongside intraperitoneal gemzar (GEM) or cyclophosphamide (CTX) treatment. multiplex immunohistochemistry (mIHC) and single analyses using 10X Genomics platform of tumor were performed for resolving the key factors in the therapeutic process. Results: Comparing the KPC-Luc-mcherry with the NL-KPC tumor, we found that non labeled KPC has the typical morphology of human PDAC, immunologically cold and is highly aggressive compared with KPC-Luc-mcherry. WST11-VTP results in high cure rate (~50%) of animals bearing small KPC-Luc-mcherry tumors, larger tumors required combinations with metronomic administration of GEM. High rate of complete necrosis (95-100%) was achieved also with the non-labled PDAC tumors but prolonged disease- free survival required combination with CTX. The mechanism of action for both tumor models involves co-generation of oxygen and NO radicals through local photoexcitation of WST11, followed by iNOS consumption and vascular break down. Infiltration of immune cells alarmed by HMGB1 and other DAMPs leads to annihilation of residual cancer cells and prolonged anticancer immunity. The administration of CTX amplifies and prolonged the VTP oxidative stress. Conclusion: WST11-VTP combination with immune modulating chemotherapeutic agents administrations, activated by endovascular illumination through the SMA, may provide solution to the unmet need of early stage diagnosed PDAC patients. (1) Franz E. Boas et al, “Downstaging Locally Advanced Pancreatic Cancer To Resectability: Perivascular Ablation Using An Intra-arterial Balloon Laser Catheter In Pigs”, Abstract Archives of the RSNA, RSNA 2021,SDR-IR-13- “Redefining radiology” 11/29-12/4, 2021 Citation Format: Lilach Agemy, Keren Sasson, Tamar Yechezkel, Dina Priese, Yaniv Cohen, Zachary Zacks, Gil Stelzer, David P. Kelsen, Hooman Yarmohammadi, Alice C. Wei, Stephen B. Solomon, Avidgor Scherz. New treatment modality for pancreatic cancer-Vascular Targeted Photodynamic therapy with WST11 (Padeliporfin) combined with endovascular light delivery [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr C016.