Most patients with Ovarian cancer do not benefit from immune checkpoint immunotherapy and thus require alternate clinical approaches. The team had previously shown that vaccination using whole tumor-pulsed dendritic cells amplifies neoantigens recognition in ovarian cancers.
This multidisciplinary study*, published in Nature Cancer, was conducted by researchers of the Lausanne Branch of the Ludwig Institute for Cancer Research; Pr George Coukos, head of the Human Integrated Tumor Immunology Engine (Hi-TIDe) and director of the Oncology department, Pr Alexandre Harari, Group leader of the T cell discovery, one of the laboratories of the Hi-TIDe, and Pr Lana Kandalaft, head of the Center of Experimental Therapeutics.
The team reports the results of a phase I trial demonstrating that neoantigens-specific T-cell responses can be further reinvigorated by the subsequent adoptive cell transfer (ACT) of autologous vaccine-primed ex vivo-expanded peripheral blood T-cells followed by vaccination.
Epitope spreading with novel neoantigen reactivities were found post-ACT in patients with clinical benefit, where circulating tumor (ct)DNA corresponding to immunogenic neoepitopes were detected, suggesting reinvigoration of tumor-sculpting immunity. In Summary, the team shows re-invigoration of antitumor immunity by ACT of vaccine-primed peripheral blood T cells with additional vaccination using whole-tumor lysate-pulsed DCs. This therapy was not sufficiently potent to eradicate tumors, yet produced clinical benefit, and important lessons can be learnt from the medium-intensity lymphodepletion and the use of CD28-costimulated cells, which enabled rapid neutrophil recovery and lymphoid reconstitution, respectively.
The research was generously supported by the Ludwig Institute for Cancer Research, the Ovacure Foundation, the Biltema Foundation, the Paul Matson Foundation and the Cancera Foundation. NIH grants R01FD003520, R21CA156224, and P50CA083638 SPORE in Ovarian Cancer, grants from the Marcus Foundation and the Ovarian Cancer Immunotherapy Initiative. Grant by the Pennsylvania Department of Health. This research is a fruitful collaboration between the Lausanne University Hospital (CHUV), the University of Lausanne (UNIL), the Center for Cell Therapy, the Center for Experimental Therapeutics, the Department of Oncology (CHUV), the Swiss Institute of Bioinformatics (SIB), the Center for Cellular Immunotherapies, the Division of Gynecologic Oncology, the Department of Radiology, University of Pennsylvania, USA
*A phase 1 trial of adoptive Transfer of autologous vaccine-primed Circulating T cells in Ovarian Cancer