Th17-inducing autologous dendritic cell vaccination promotes antigen-specific cellular and humoral immunity in ovarian cancer patients

Matthew S. Block (), Allan B. Dietz, Michael P. Gustafson, Kimberly R. Kalli, Courtney L. Erskine, Bahaaeldin Youssef, Geraldine V. Vijay, Jacob B. Allred, Kevin D. Pavelko, Michael A. Strausbauch, Yi Lin, Megan E. Grudem, Aminah Jatoi, Carolyn M. Klampe, Andrea E. Wahner-Hendrickson, S. John Weroha, Gretchen E. Glaser, Amanika Kumar, Carrie L. Langstraat, Mary L. Solseth, Michael C. Deeds, Keith L. Knutson () and Martin J. Cannon ()
Additional contact information
Matthew S. Block: Mayo Clinic
Allan B. Dietz: Mayo Clinic
Michael P. Gustafson: Mayo Clinic
Kimberly R. Kalli: Mayo Clinic
Courtney L. Erskine: Mayo Clinic
Bahaaeldin Youssef: Mayo Clinic
Geraldine V. Vijay: Mayo Clinic
Jacob B. Allred: Mayo Clinic
Kevin D. Pavelko: Mayo Clinic
Michael A. Strausbauch: Mayo Clinic
Yi Lin: Mayo Clinic
Megan E. Grudem: Mayo Clinic
Aminah Jatoi: Mayo Clinic
Carolyn M. Klampe: Mayo Clinic
Andrea E. Wahner-Hendrickson: Mayo Clinic
S. John Weroha: Mayo Clinic
Gretchen E. Glaser: Department of Obstetrics and Gynecology
Amanika Kumar: Department of Obstetrics and Gynecology
Carrie L. Langstraat: Department of Obstetrics and Gynecology
Mary L. Solseth: Mayo Clinic
Michael C. Deeds: Mayo Clinic
Keith L. Knutson: Mayo Clinic
Martin J. Cannon: University of Arkansas for Medical Sciences

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract In ovarian cancer (OC), IL-17-producing T cells (Th17s) predict improved survival, whereas regulatory T cells predict poorer survival. We previously developed a vaccine whereby patient-derived dendritic cells (DCs) are programmed to induce Th17 responses to the OC antigen folate receptor alpha (FRα). Here we report the results of a single-arm open-label phase I clinical trial designed to determine vaccine safety and tolerability (primary outcomes) and recurrence-free survival (secondary outcome). Immunogenicity is also evaluated. Recruitment is complete with a total of 19 Stage IIIC-IV OC patients in first remission after conventional therapy. DCs are generated using our Th17-inducing protocol and are pulsed with HLA class II epitopes from FRα. Mature antigen-loaded DCs are injected intradermally. All patients have completed study-related interventions. No grade 3 or higher adverse events are seen. Vaccination results in the development of Th1, Th17, and antibody responses to FRα in the majority of patients. Th1 and antibody responses are associated with prolonged recurrence-free survival. Antibody-dependent cell-mediated cytotoxic activity against FRα is also associated with prolonged RFS. Of 18 patients evaluable for efficacy, 39% (7/18) remain recurrence-free at the time of data censoring, with a median follow-up of 49.2 months. Thus, vaccination with Th17-inducing FRα-loaded DCs is safe, induces antigen-specific immunity, and is associated with prolonged remission.

Date: 2020
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DOI: 10.1038/s41467-020-18962-z

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