A. A. Maawy1, Y. Hiroshima4, Y. Zhang3, M. Garcia-Guzman5, L. Makings5, R. Heim5, G. A. Luiken2, R. M. Hoffman1,3, M. Bouvet1 1University Of California – San Diego,Surgery,San Diego, CA, USA 2OncoFluor, Inc.,San Diego, CA, USA 3AntiCancer, Inc.,San Diego, CA, USA 4Yokohama City University,Surgery,Yokohama City, , Japan 5Aspyrian Therapeutics,San Diego, CA, USA
Introduction: Photoimmunotherapy (PIT) is a selective treatment modality in the treatment of cancer. Tumor selectivity and targeting is based on the use of a monoclonal antibody specific to cancer epitopes conjugated to a near infra red (NIR)phthalocyanine dye (IR700). While surgical resection of pancreatic cancer offers the only real chance at a cure, recurrence rates and overall mortality is still high. PIT, if efficacious, could serve as a useful adjunct in the surgical treatment of pancreatic cancer that would help eliminate invisible microscopic disease on the tumor bed. In this study, we chose to use anti-carcinoembryonic antigen (CEA) as the monoclonal antibody because it highly expressed in pancreatic cancer.
Methods: Athymic nude mice were orthotopically implanted with the GFP expressing human pancreatic cancer cell line BxPC3. After engraftment, the mice were divided into two groups: Bright light surgery (BLS) + anti-CEA-IR700 + 690nm laser (PIT) and BLS only. The anti-CEA-IR700 conjugate (100 μg) was administered to the treatment group via tail vein injection 24 hours prior to therapy. After 24 hours, tumors were surgically exposed and treated with the designated phototherapy intraoperatively at an intensity of 150 mW/cm2 for 30 minutes and serially imaged non-invasively for 8 weeks using the OV-100 small animal imager.
Results: Over the course of 8 weeks there was a significant difference in tumor size between the PIT-BLS (2.14 mm2, 95% CI [6.34, -2.06] and BLS group (115.2 mm2, 95% CI [141.6, 88.8]) with p<0.001. There was also a significant difference in tumor weight between the PIT-BLS (6.65 mg, 95% CI [19.65, -6.35] and BLS (1100 mg, 95% CI [1406, 794] at 8 weeks with p<0.001. In the PIT-BLS group, there was no tumor detectable in 86% of the mice vs a 100% recurrence rate in the BLS group (p=0.04).
Conclusion: PIT causes significant tumor cell death with high specificity in the treatment of pancreatic cancer as a surgical adjuvant in orthotopic nude mouse models. Animals treated with BLS-PIT appear to be cured from an aggressive metastatic pancreatic cancer. PIT holds promise in the treatment of this highly lethal cancer and may serve as a useful adjunct to surgery in the eradication of otherwise undetectable microscopic disease. The results of the present report suggest that BLS-PIT be evaluated clinically in the future.
