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.