[42] Cancer Immunotherapy

The use of our immune system to fight cancer (immunotherapy) is a promising strategy and spectacular results have been obtained in the last years. The objective of our laboratory is to implement such approaches for the treatment of glioma (brain tumors), a disease for which current treatments are of limited efficacy. We are pursuing three main research axes:

Development of therapeutic vaccines

One of the key steps in the development of immunotherapy for glioma was the identification of a set of glioma antigens by our group in 2012, using peptide elution from human glioma samples, results published in 2012. In 2013, we initiated a clinical trial testing this vaccine (called IMA950) combined with the poly-ICLC adjuvant in patients suffering from the more severe form of glioma, glioblastoma. This study showed that CD4 and CD8 T cell response to the vaccine were elicited. Analysis of tumor samples and of their composition in immunosuppressive cells is ongoing and will allow identification of prediction makers for vaccine efficacy.

Based on these results, we are now (November 2018) starting a clinical trial in patients suffering from progressive glioblastoma, combining the IMA950/poly-ICLC vaccine with the immune checkpoint antibody PD-1. This vaccine will be injected before a second surgery, allowing analyzing T cell responses at the tumor site and identifying parameters promoting efficient antitumor vaccination.

The proof-of-concept of the efficacy of peptide elution for identification of relevant glioma antigens offered the possibility to use the same approach to identify glioma antigens in a personalized way. This project (the GAPVAC project) received important funding from the European Community (FP7), allowing in 2014 the initiation of a large multicentric study in Europe, co-lead by Pierre-Yves Dietrich.

Development of CAR T cell therapy

Our work on glioma antigen identification offers the opportunity to develop cell therapy for glioma. The CAR (chimeric antigen receptor) approach involves expressing an antitumor antibody at the T cell surface, allowing redirection of the T cell to the tumor. The identified glioma antigens are ideal target for this approach, allowing the design of multiple anti-glioma CARs. In collaboration with the group of Prof. Carl June in the University of Pennsylvania, we are developing this approach for glioma. We hope to start the first clinical trials in patients in the next few years.

The glioma tumor microenvironment

Optimization of glioma immunotherapies must take into consideration the very special features of the brain. Indeed, glioma occurs in an organ surrounded by the blood-brain barrier and bathed into multiple immunosuppressive factors, among others. This implies that the initiation and regulations of antitumor immune responses follow particular rules. We are therefore investigating the glioma tumor microenvironment, using flow cytometry and gene expression analysis. This will allow identifying parameters that will need to be targeted to achieve efficient glioma immunotherapy.

In addition, the future establishment of our lab in the Agora and the Swiss Cancer Center Léman will be the opportunity to develop our research activity in new glioma-related projects.