Martin Cannon, PhD, discusses the use of dendritic cell vaccines and immune checkpoint inhibitors in ovarian cancer.
Martin Cannon, PhD, professor, microbiology and immunology, the University of Arkansas for Medical Sciences (UAMS), UAMS College of Medicine, discusses the use of dendritic cell vaccines and immune checkpoint inhibitors in ovarian cancer.
In a phase 1 trial (NCT01606241), investigators assessed a Th17-stimulating dendritic cell vaccine in the maintenance setting in patients with stage IIIC or IV ovarian cancer following completion of upfront surgery and chemotherapy, generating encouraging responses. During the phase 1 trial's progress, investigators considered next steps and laid the foundation for a phase 2 trial, which is on the horizon in the same patient population, Cannon says. This phase 2 trial will randomly assign patients in a 2:1 ratio to receive either the dendritic cell vaccination or placebo, he explains. Notably, the focus will be on patients who wouldn't typically receive maintenance PARP inhibitors, Cannon adds. Patients with BRCA wild-type or homologous recombination–proficient ovarian cancer have a significant clinical need, as they possess robust DNA repair mechanisms, which make them less likely to benefit from treatment with olaparib (Lynparza) or niraparib (Zejula), Cannon emphasizes.
Looking to the future, concerns have come up regarding the use of dendritic cell vaccination with immune checkpoint inhibition. Investigators aimed to better understand whether Th17 vaccination could enhance responses to PD-1 inhibition in ovarian cancer mouse models, Cannon expands. Findings indicated that PD-1 inhibition alone had minimal effects on ovarian cancer models, mirroring clinical experiences, Cannon says. Although Th17 vaccination aloneextended survival, the combination of the vaccination and PD-1 inhibition significantly extended survival rates, he notes.
The next logical step is to design a clinical trial involving vaccination in conjunction with pembrolizumab (Keytruda). Investigators have received support from the National Cancer Institute for this potentially upcoming trial, Cannon continues. This research could enhance the clinical efficacy of immune checkpoint inhibitors, he adds. Overall, there are numerous avenues to explore for stimulating T-cell responses and providing support for immune checkpoint inhibition in ovarian cancer, Cannon concludes.