Immunomonitoring during active-specific immunotherapy in pancreatic and colorectal cancer

Background: Until recently, most clinical clinical vaccine trials in humans have been performed without immunomonitoring. The effect of active specifi c immunotherapy was evaluated mainly by clinical follow-up and diagnostic i maging. Immunological effects that might be induced by the vaccine were not measured. In this report, we describe a method for flow cytometry analysis of anti-GA733 antibodies in the serum of patients undergoing immunotherapy with baculovirus-derived extracellular domain of the GA733/CO 17- 1A antig en, a cell. surface glycoprotein expressed by more than 80% of human colore ctal and pancreatic carcinomas and liver metastases. Methods: 5 pancreatic and 7 colorectal cancer patients received 4 weeks aft er tumor resection the first injection of the vaccine subcutaneously (50, 2 00 and 800 mu g/injection pins aluminiumhydroxide as adjuvans) monthly for 4-7 months. Serum was collected before the first vaccination and 2 weeks af ter each further vaccination. Plow cytometry was performed using the colore ctal carcinoma cell line SW1116 as target for specific anti-GA733 antibodie s. Results: After 4 to 7 vaccinations maximal increase in specific antibodies was for colorectal carcinoma 1.5 fold (median; min 0, max 4.6), for pancrea tic cancer 2.7 fold (0-6.8). This antibody peak was not significantly incre ased in colorectal cancer (Scheffe test p = 0.12) but in pancreatic cancer (p = 0.014). The antibody titers in pancreatic cancer compared to colorecta l cancer before immunotherapy (29.7% vs 5.8 %, p = 0.039) as well as the an tibody peak (34% vs 7.7%, p = 0.014) were significantly increased. Conclusion: The immunomonitoring during a phase I/II study with novel GA733 vaccine is practicable and shows a reduced immunogenicity of the vaccine i n colorectal carcinoma, whereas specific antibody titers were existing in p ancreatic carcinoma. Before clinical evaluation in a phase III study, immun ogenicity needs to be enhanced by stronger adjuvants, cytokines or antigen- preparations.