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Home » Onderzoek/Research » Tumor Viruses and Cancer Immunotherapy

3.D Tumor Virology and Cancer Immunotherapy

Our main objective is to develop strategies for the immunotherapeutic treatment of virus-induced cancer. In the past years we focused on the immunotherapy of cervical cancer. We recently initiated a novel research line on the development of a therapeutic immunization against liver cirrhosis or cancer induced by chronic Hepatitis C virus (HCV) infection. The central aim of these strategies is to induce a strong cellular immune response against the tumor involved. For cervical cancer the tumor antigens aimed for are the E6 and E7 proteins of Human Papillomavirus (HPV), the virus involved in the development of this type of cancer. For liver cancer and cirrhosis, we aim at the induction of an HCV-specific immune response. Apart from these virus-induced tumors we are involved in clinical studies on the immunotherapy of ovarian cancer. Several approaches are being pursued including genetic immunization with recombinant suicide viral vectors based on Semliki Forest virus and immunization with antigen-containing virosomes (pre-clinical studies), and long peptide-based immunization (clinical trials).

 

Pre-clinical studies

Semliki Forest virus-based immunotherapy
For the SFV-based immunization, several constructs have been generated encoding HPV16 E6 and E7 protein antigens, cytokine and reporter genes. Presently we are generating HCV constructs. To evaluate the efficacy of the immunization experiments, we established a diversity of immunological read-out systems. In addition, in vivo (immuno)therapeutic studies are being performed using murine (transgenic) tumor models. In the past years we thus demonstrated the enormous potency of this vector system in inducing long-term cellular immune responses and complete regression of established tumors in mice. We currently study the mechanism of action of these immunization strategies in more detail. In the near future, this SFV-based immunization will be evaluated in clinical trials (see clinical trials).

 

Clinical studies

Immunomonitoring of natural responses and responses induced by standard treatment

In collaboration with Prof. dr. Hans Nijman (Department of Gynaecology and Obstetrics, UMCG), we study the role of cell-mediated immunity against HPV and P53 in the control of (pre)malignant cervical cancer and ovarian cancer, respectively. In these (longitudinal) studies immune responses and immune effector cells in blood-, tumour- and lymph node samples of patients before, during the course of the treatment (surgery and/or radio chemotherapy) and at several time points after treatment are being characterized.

 

Clinical trials

Several clinical trials have been conducted in direct collaboration with Prof dr Nijman and Prof dr van der Zee (UMCG), Prof. dr. Cees Melief and Prof. Dr. Sjoerd van de Burg (LUMC) and ISA Pharmaceuticals. The department of Molecular Virology conducted the   immunomonitoring of the responses. In 2006-2009 two P53 long-peptide immunization trials in ovarian cancer patients were conducted and monitored. These trials demonstrated the safety of the immunization, while furthermore cellular immune responses were induced in all patients.

Within the context of a start-up biotech company “ViciniVax” we are setting up a phase 1/2 clinical trial with SFV-eE6,7 in patients with premalignant HPV lesions. We anticipate to initiate this clinical trial early 2013.

 

 

 

Principal investigator

Toos DaemenToos Daemen
Prof. dr.,
Professor of Tumor Virology

Tel: +31.(0)50 363 2723
Mail: Toos Daemen

 

Research staff

Georgia Koutsoumpli, PhD student
Maartje Wouters, PhD student
Stephanie van der Wall, PhD student
Baukje-Nynke Hoogenboom, Research Technician
Annemarie Boerma, Research Technician
Jolanda Oldengarm-Leidelmeijer, staff assistant

 

Postadres:
University Medical Center Groningen
Department Medical
Microbiology – Virology & Immunology Research
hpc EB 88
Hanzeplein 1
9713 GZ Groningen
Postbus 30.001
9700 RB Groningen Nederland

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