Although PD-1 checkpoint inhibition has improved outcomes for some cancer types, a substantial proportion of solid tumors still do not respond, in part due to inadequate cytotoxic CD8+ T-cell infiltration and survival within the tumor microenvironment (TME). CD25+ regulatory T-cells (Tregs) are a subset of T-cells that play a key role in suppressing CD8+ T-cell activity. Depletion of Tregs in the TME could thus enhance anti-cancer immune responses. Here, we present the experience of a patient with platinum-resistant ovarian carcinoma who achieved a durable partial response on a phase 1 clinical trial of an anti-CD25 antibody-drug conjugate combined with pembrolizumab. Notably, her tumor response correlated with a reduction in CD25+ Tregs on paired tumor biopsies and further deepened after treatment discontinuation. This case provides early proof-of-concept that Treg depletion combined with PD-1/PD-L1 inhibitors can lead to anti-cancer efficacy in refractory diseases and offers key lessons to guide future development of anti-Treg therapeutics.
Keywords: Immunotherapy; cancer immunology; case report; checkpoint inhibitors; clinical immunology; ovarian cancer.
We report here a case of a patient with refractory ovarian cancer who had a durable and meaningful response to experimental immunotherapy drugs, a response that continued even after the drugs were stopped. The drugs were designed to deplete an immune cell population known as T-regulatory cells. In all, 5 out of the 17 ovarian cancer patients treated with this regimen had tumor shrinkage. Drugs against T-regulatory cells should be further studied in ovarian and other cancers.