Martin Cannon, PhD, discusses the phase 1 investigation of the Th17 dendritic cell vaccine in ovarian cancer, and how it could potentially improve suboptimal responses when treated with immunotherapy alone in this population.
Martin Cannon, PhD, professor, Department of Microbiology and Immunology, University of Arkansas for Medical Sciences (UAMS) College of Medicine, discusses the phase 1 investigation of the Th17 dendritic cell vaccine in ovarian cancer, and how it could potentially improve suboptimal responses when treated with immunotherapy alone in this population.
A correlation between Th17 cell infiltration and prolonged overall survival in patients with ovarian cancer patients was identified in previous research, prompting interest in harnessing Th17 cells. Accordingly, a Th17-stimulating dendritic cell vaccine was developed to potentially improve immune responses and clinical outcomes in this space, Cannon begins.
The immunogenicity and safety of the Th17-stimulating dendritic cell vaccine in patients with stage IIIC–IV ovarian cancer was evaluated in a single-arm, open-label, phase 1 clinical trial (NCT02111941), Cannon details. Patients received the dendritic cell vaccine in the maintenance setting following the completion of upfront surgery and chemotherapy, he says. Primary end points of the phase 1 trial include safety and tolerability, with recurrence-free survival (RFS) and immunogenicity as secondary end points. Of the 19 patients enrolled on the study, 18 were evaluable.
Cannon notes that when the study was designed, strategies in the maintenance setting involved the cessation of treatment for 12 to 18 months, while the patient was monitored for recurrence, at which point treatment would resume. However, the approvals for, and increasing use of, PARP inhibitors in the maintenance setting has since changed this approach, he adds.
Initial results from the study were reported in 2020, and demonstrated that vaccination with Th17-inducing folate-receptor alpha (FRα)–loaded dendritic cells was safe, generated antigen-specific immunity, and was associated with increased remission, Cannon reports. A comparison of T-cell frequency before and after vaccination showed that the vaccine successfully stimulated Th1, Th17, and antibody responses to FRα in most patients with ovarian cancer.
Moreover, Th1 and FRα antibody responses were associated with high RFS, Cannon says. The median RFS with the vaccine was 12.1 months, and the median overall survival (OS) was not reached. At a median follow-up of 49.2 months, the recurrence-free survival rate was 38.9% in at-risk, efficacy evaluable patients. Regarding safety, the vaccine was well tolerated and produced transient, low-grade adverse effects (AE) primarily caused by injection site reactions.