Ludwig Lausanne’s Sara Bobisse, Lana Kandalaft, Alexandre Harari and director George Coukos reported in Nature Cancer in September that combining adoptive T cell therapy with a personalized, dendritic cell cancer vaccine under development at the Branch can benefit patients with late-stage, drug-resistant ovarian cancer. The researchers analyzed responses to the combination therapy in patients who had previously participated in a clinical trial evaluating a regimen that included the vaccine. In this study—done, as before, in partnership with researchers at the University of Pennsylvania—those patients received an infusion of their own vaccine-primed, circulating T cells followed by multiple periodic doses of personalized vaccines. The combination vaccine-adoptive T cell therapy (ACT), which was found to be generally safe, yielded control of the disease within three months in 12 of 17 patients. Though this was not a double-blind, placebo-controlled trial, the study recorded a median overall survival time of 14.2 months for patients who completed the regimen, compared to a median historical survival of six months or less for comparable patients receiving fourth- and fifth-line chemotherapy. The researchers also showed that T cells targeting the neoantigens were reinvigorated by the combination therapy and correlated with positive patient responses to the treatment. Further, DNA sequences encoding neoantigens targeted by the T cells were found at higher levels in circulating tumor DNA, suggesting a vaccine-directed attack against cancer cells.
A phase 1 trial of adoptive transfer of vaccine-primed autologous circulating T cells in ovarian cancer
Nature Cancer, 2023 September 21