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
Current Drug Delivery
Title: The Use of Specific Monoclonal Antibodies to Target Immunogenic Tumor Membrane Proteins in Patients with Recurrent Pancreatic and Colon Cancer
Volume: 9 Issue: 1
Author(s): Myron Arlen, XuePing Wang, Janos Luka, Rishab Gupta, Olga Saric and Philip M. Arlen
Affiliation:
Keywords: Monoclonal antibodies, immunotherapy, pancreatic and colon cancer, immunogenic membrane proteins, ADCC
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.
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Cite this article as:
Arlen Myron, Wang XuePing, Luka Janos, Gupta Rishab, Saric Olga and M. Arlen Philip, The Use of Specific Monoclonal Antibodies to Target Immunogenic Tumor Membrane Proteins in Patients with Recurrent Pancreatic and Colon Cancer, Current Drug Delivery 2012; 9 (1) . https://dx.doi.org/10.2174/156720112798376087
DOI https://dx.doi.org/10.2174/156720112798376087 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
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