gms | German Medical Science

Introduction: Patients with pancreatic carcinoma have a grim prognosis. They are often diagnosed in late stages of the disease and are hard to treat. Immunotherapy of tumors has been an intriguing field of research with mentionable breakthroughs. Here, we test the possibility of inducing an in vitro antibody response against pancreatic carcinoma antigens. We analyze the specificity and overall characteristics of the elicited humoral response and test its binding capacity with regard to 5 pancreatic carcinoma cell (PCC) lines.

Material and methods: Plasma membrane fragments (PMFs) of five cultured PCCs were isolated and added to cultures of isolated peripheral blood mononuclear cells (PBMCs) from healthy volunteers (n=8) for 14 days. To simulate T-cell signaling, we added IL-21, IL-4 and anti-CD40 mAB. Using ELISAs, we tested the quantity and specificity of IgG formed against PMFs and the intact PCCs they originated from. To visualize human antibody binding to tumor cell surface antigens on human PCCs, we used a fluorescent anit-human-IgG-antibody.

Results: IgG were formed in all cases. There was an increase of quantity when T-cell signaling was simulated, though this did not reach significance. Interestingly, significantly less IgG was produced by PBMCs presented with tumor antigens except in the cases of PANC-1 and MIAPACA when T-simulation was added (p<0.05). PMFs from PANC-1 cells elicited significant and specific IgG formation against PANC-1-PMFs in comparison to the control (p=0.026). Additionally, simulation of T-cells had a significant impact on binding of these antibodies to tumor cell anigens (p=0.019). However, using a hole cell assay IgG binding to intact PCCs was not observed unanimously (p=0.66), yet it was observed in individual cases. We were able to visualize cell surface binding by immunofluorescent staining.

Conclusion: Humoral immune response with tumor antigens and T-cell simulation can be induced in vitro. This response has potential to generate antibodies specific to tumor antigens.