Tumor-associated stroma cell therapy in patients with pancreatic cancer potentiates therapeutic effect of tumor B-cell hybrid (TBH) auto-vaccines

Abstract

4569 Background: Pancreatic Cancer (PC) tumor-associated stroma cells play an important role in PC’s immune surveillance escape. Secretion of Transforming Growth Factor β (TGFβ) and IL10 by PC tumor cells disturb the antigen presenting function of the stroma cells. It may explain the poor results of most immunotherapeutic approaches. Granger et al. reported a successful approach for treating small size pancreatic tumors, namely Mixed Lymphocyte Culture (MLC) cytoimplant. MLC cytoimplants, acting as a Th1 cytokine pump inside the tumor, are thought to revert the tumor-associated stroma cell dysfunction, and facilitate an immune attack. In view that TBH auto-vaccines have modest activity in advanced PC, we considered the possibility that a combination of MLC cytoimplant and TBH vaccines might potentiate the immune response. In this study we compared the response of MLC cytoimplant, TBH vaccines, and combinations of both therapies. Methods: 40 patients with advanced PC were treated: Group 1 MLC cytoimplan (10); Group 2 TBH vaccines (3); Group 3 one MLC cytoimplant and three TBH vaccines (9); Group 4 one MLC cytoimplant and six TBH vaccines (12) and Group 5 one MLC cytoimplant followed by two TBH immunizations, then second MLC cytoimplant followed by 4 TBH vaccines (6). Anti-tumor immune response was measured by Lymphocyte proliferation assay against autologous PC. Results: MLC cytoimplant combined with TBH vaccines appears to have synergistic and effective anti-tumor activity in advanced PC. Kaplan Meyer analysis showed a significant difference in the survival of group 4 as compared with the other four groups (P<0.001). After cytoimplant administration, 1/12 patients in Group 4 and 1/6 patients in Group 5 experienced transient bleeding episodes (lasting less than 12 hours). After the second MLC cytoimplant, all patients in Group 5 developed significant Graft Vs Host Disease (GVHD), an occurrence that probably contributed to the Group’s shorter survival when compared to Group 4’s survival. Conclusions: The observation that a second MLC cytoimplant leads to GVHD is consistent with a pro-inflammatory change in the tumor-associated stroma cells. MLC cytoimplant followed by TBH vaccines appear to prolong survival. No significant financial relationships to disclose.