The Use of Specific Monoclonal Antibodies to Target Immunogenic Tumor Membrane Proteins in Patients with Recurrent Pancreatic and Colon Cancer

Myron      Arlen; XuePing      Wang; Janos      Luka; Rishab      Gupta; Olga      Saric; Philip      M. Arlen

doi:10.2174/156720112798376087

Abstract

Tumor associated antigens from pooled allogeneic membrane proteins were isolated, partially purified and tested as a possible vaccine in patients with stage II and III colon cancer. The vaccine, when given in combination with an adjuvant following surgical resection, resulted in marked improvement in survival compared to control patients having only undergone surgical resection of their tumor. While it was possible to demonstrate that patients receiving vaccine turned on both humoral and cell mediated responses, it appears that survivors remaining free of disease at 5-7 yrs post op were able to mount a strong IgG1 response as the primary mechanism for tumor destruction. Antibodies from hybridomas made against the vaccines resulted in production of monoclonals with a high degree of ADCC. Those monoclonals targeting pancreatic cancer and in particular the MUC5ac mutated antigen representing tumor immunogen were studied in detail. Animal models indicated rapid tumor destruction when nude mice, injected with human pancreatic cancer were then immunized with NPC-1 monoclonal antibody targeting mutated MUC5ac. FDA studies including tissue cross reactivity, biodistribution, and cytokine release assays indicated safety and efficacy of the monoclonals we have developed. Submission of the IND allowed for initiation of the Phase I trial using mAb NPC-1 targeting pancreatic cancer when that antigen was found to be expressed.

Keywords: Monoclonal antibodies, immunotherapy, pancreatic and colon cancer, immunogenic membrane proteins, ADCC

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