NPJ Vaccines publishes the results of research led by Alexandre Harari and Lana Kandalaft (first authors: J. Tanyi & C.Chiang).
The group, part of the Ludwig Lausanne branch, demonstrated that the combinatorial use of a personalized tumor lysate-pulsed dendritic cell vaccine (OCDC), bevacizumab, cyclophosphamide, acetylsalicylic acid and low-dose interleukin-2 is efficacious in a recurrent advanced OC phase I trial (NCT01132014). Vaccine-specific T cell responses were elicited and these were positively correlated with patients’ prolonged time-to-progression and overall survival.
In the mouse ID8 ovarian model, animals receiving the same regimen showed prolonged survival, increased tumor-infiltrating perforin-producing T cells, increased neoantigen-specific CD8+ T cells, and reduced endothelial Fas ligand expression and tumor-infiltrating T regulatory cells. This combinatorial strategy equally highlighted the predictive value of ID8 model for ovarian trial development. The results are published in NPJ Vaccines.
A word from the first-author...
"We provided evidence in both patients and mouse ID8 ovarian tumor model that the personalized DC vaccine that was created is able to elicit tumor neoantigen responses. In the ID8 ovarian model, we are able to correlate specific tumor neoantigens to reduced tumor growth. As neoantigens are unique to each patient, we can potentially use our DC vaccine to elicit tumor neoantigen-responses in the patient and further amplify them with the treatment modalities we have described in our study.
In the same study, we demonstrated that in the ID8 tumor model we could use immunomodulatory therapies (as the ones we used in our study, i.e. bevacizumab, cyclophosphamide, acetylsalicylic acid and low-dose interleukin-2) and modulate the tumor microenvironment to make it more conducive for cancer vaccination. These agents are already approved for use in different cancer indications with established safety records. Hence, these treatment modalities could potentially be applied to different cancer types." (Lai-Lai Cheryl Chiang)
- This work was supported by National Cancer Institute P01-CA83638 Ovarian Specialized Program of Research Excellence (SPORE), the Immunotherapy Initiative for Ovarian Cancer (ITI-OC), Markus Foundation, Rivkin Center for Ovarian Cancer, Research Foundation for the Treatment of Ovarian Cancer, Inc, the Ludwig Institute for Cancer Research and institutional support from the Centre Hospitalier Universitaire Vaudois (CHUV).