Following primary therapy of high-grade ovarian tumors, 18 patients with minimal residual disease were vaccinated with autologous, Th17-biased DCs pulsed with peptides from folate receptor alpha (FRα), an ovarian cancer-associated antigen. No dose-limiting toxicities were observed, and the majority of patients developed FRα-specific IFNγ+ and IL-17+ T cell responses and antibodies. Seven patients (~39%) who did not experience disease recurrence had higher antibody and IFNγ+ (but not IL-17+) T cell responses than recurring patients, whose later disease was associated with a reduction of intratumoral Tregs and increase in PD-L1.
Contributed by Alex Najibi
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 (FR_). 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 FR_. 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 FR_ in the majority of patients. Th1 and antibody responses are associated with prolonged recurrence-free survival. Antibody-dependent cell-mediated cytotoxic activity against FR_ 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 FR_-loaded DCs is safe, induces antigen-specific immunity, and is associated with prolonged remission.
Author Info: (1) Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA. block.matthew@mayo.edu. (2) Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905,
Author Info: (1) Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA. block.matthew@mayo.edu. (2) Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA. (3) Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA. (4) Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA. (5) Department of Immunology, Mayo Clinic, Rochester, MN, 55905, USA. (6) Department of Immunology, Mayo Clinic, Jacksonville, FL, 32224, USA. (7) Department of Immunology, Mayo Clinic, Jacksonville, FL, 32224, USA. (8) Mayo Clinic Cancer Statistics, Mayo Clinic, Rochester, MN, 55905, USA. (9) Immune Monitoring Core, Mayo Clinic, Rochester, MN, 55905, USA. (10) Immune Monitoring Core, Mayo Clinic, Rochester, MN, 55905, USA. (11) Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA. (12) Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA. (13) Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA. (14) Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA. (15) Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA. (16) Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA. (17) Department of Obstetrics and Gynecology, Rochester, MN, 55905, USA. (18) Department of Obstetrics and Gynecology, Rochester, MN, 55905, USA. (19) Department of Obstetrics and Gynecology, Rochester, MN, 55905, USA. (20) Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA. (21) Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA. (22) Department of Immunology, Mayo Clinic, Jacksonville, FL, 32224, USA. knutson.keith@mayo.edu. (23) Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA. cannonmartin@uams.edu.
