Program 2 / WP3
Potentiation of monoclonal antibodies for the treatment of patients with cancer
Pr Charles Dumontet – Anticancer Antibody Team
Monoclonal antibodies are increasingly used in oncology, both in hematological malignancies such as lymphoma and solid tumors such as breast cancer and colon cancer.
These molecules are produced in vitro and are usually better tolerated than chemotherapy, with which they can be combined. The mechanisms of action of monoclonal antibodies are still poorly understood and include both a direct effect of the antibody on tumor cells and the recruitment of cells from the patient’s immune system.
In the scope of the LYric project our team, the Anticancer Antibody Team, seeks to enhance the effect of the immune system in order to increase the anticancer effect of monoclonal antibodies. To this end we analyze the relationships between different cells from the immune system and antibodies. We evaluate the possibility to stimulate certain types of white blood cells in order to make them more active against tumor cells.
Our first results in preclinical models are quite promising and may allow clinical trials in patients in the next few years.
Program 2 / WP3
Analyze of tumoral and cellular immune responses in paraneoplasic syndromes: a successful anti-tumor immune response
Paraneoplastic cerebellar degeneration (PCD) are rare neurological syndromes associated with cancer but without tumor cells in the brain. PCD are mainly observed in women with breast or ovarian tumors. These women harbor autoantibodies called anti-Yo that recognize an antigen, called CDR2, expressed both in cerebellum neurons and in the tumor cells. Tumor evolution in patient with PCD is believed to be more indolent than the same group of tumor in patients without PCD. This observation could be explained by the immune response against the antigen CDR2 expressed by the tumor. The molecular mechanisms responsible for this natural anti-tumoral immune response are unclear but are probably related to overexpression of genes associated with tumor type and tumor-associated immune response. Our objective is to characterize the ovarian cancer associated with anti-Yo PCD and to compare them with the same type of ovarian cancer in patients without PCD.
We collected 26 ovarian tumour samples from patients with anti-Yo-associated PCD using the database of the French Paraneoplastic Neurological Syndrome reference Center. Samples were sent by referral pathologist of the Centre Léon Bérard. Our project is now to characterize these ovarian cancers and study different tumoral and immune response markers expression by immunohistochemistry as well as to identify particular molecular profile by genomics approach. These results will be compared to a control group of 52 ovarian cancers.
Program 3 / WP4
This emerging program of the image guided local treatment program aims to develop an innovative and non-invasive HIFU treatment for liver tumor.
By using previous preclinical studies on HIFU treatment of hepatic metastasis, we seek to develop an extracorporeal treatment procedure, without surgery and puncture-free. One application is the treatment of liver primary tumor (hepatocellular carcinoma). Ultrasound imaging will guide the HIFU probe and will allow to identify the treatment zone. As tumor is moving due to the respiratory motion, real-time guidance and HIFU waves control will be developed. A first HIFU device has been developed following this principle. Preliminary in-vitro trials confirmed that a complete non-invasive treatment of liver cancer is possible.
Human and Social Sciences, in partnership with the International Agency for Research on Cancer
Testicular cancers are the most common cancers in men aged between 15 and 44 years in industrialised countries. Even if aetiologies remain unclear, the rapid incidence increase over the 30 past years, spatial variation between neighbouring countries and evolution of incidence in migrants suggest environmental risk factors. A recent hypothesis includes testicular cancer as part of testicular dysgenesis syndrome (TDS) which suggests an impact of endocrine disruptors during intra-uterine development. However, studies exploring intrauterine exposures are rare given the methodological difficulties involved.
In this context, the CLB and IARC have created a partnership aiming to investigate occupational and environmental exposures to pesticides and other pollutants in relation to the risk of testicular cancer. Three major projects are conducted as joint PhD projects supervised by Joachim Schüz and Beatrice Fervers:
- SIGEXPO: Geographic Information Systems in pesticide exposure prediction – validation study
- TESTIS Project: Case-control study in France to investigate the early environmental exposures during critical windows and gene-environment interaction with the risk to develop germinal testicular cancer.
- NORD- TEST: Registry-based case-control study in Scandinavian countries (Sweden, Denmark, Norway and Finland) aiming to measure the association between parental occupational exposures during pregnancy or before conception with the risk of developing testicular cancer in the offspring later in life.