Attenuated therapy of disseminated pancreatic cancer generates long-lasting immunity to pancreatic cancer.

We have recently reported that treatment of disseminated pancreatic cancer with an attenuated uracil auxotroph vaccine promoted antitumor CD8 T cell responses and long-term survival. Here, we optimized the treatment strategy for disseminated pancreatic cancer and show that attenuated therapy stimulated effective long-term immunity to pancreatic cancer through mechanisms involving CD4 T cells and pancreatic tumor-specific IgG. Our results suggest that cell-mediated immunity in conjunction with humoral antibody immunity may offer greater resistance to recurrence of highly aggressive tumors. Cancer immunotherapeutic strategies using attenuated vaccines merit further investigation as a novel strategy to reawaken immunity to primary pancreatic carcinoma and to generate long-lasting immunity to pancreatic cancer recurrences.