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

ABSTRACT

We have recently reported that treatment of disseminated pancreatic cancer with an attenuated Toxoplasma gondii 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 Toxoplasma gondii 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 Toxoplasma gondii 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.

KEYWORDS:

• Humoral immunity
• immunotherapy
• pancreatic cancer
• T cell protection
• Toxoplasma gondii
• tumor-specific antibodies

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

We would like to thank DartLab for flow cytometry instrument resources. The authors would also like to thank Charles Sentman and Edward Usherwood for advice.

Funding

This work was supported by NIH grant AI041930 to DJB.