Therapeutic vaccination and expression profiling group
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Nicolas Van
Baren, Clinical Investigator
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The group designs and carries out clinical trials that investigate cancer vaccines based on tumor-specific antigens called MAGE. These trials that investigate either peptides or proteins or recombinant vaccines have been completed or are ongoing. They focus mainly on patients with melanoma. The current results indicate that these vaccines are well tolerated by the patients, and are associated with regression of metastatic lesions in a minority of them. In some cases, an immune response to the vaccine has been detected in the blood of vaccinated patients. However, a close relationship between clinical and immunological responses remains to be proven. New types of vaccines are being investigated.
Moreover, the group uses the technique of microarrays to analyse the gene expression profiling of tumoral takings from patients vaccinated. The aim is to study the interactions between the cancerous cells and the immune cells in the tumor, in order to understand better the mechanisms of tumor regressions linked to the vaccinations, and why those mechanisms do not work in the majority of the vaccinated patients.
Clinical TrialsWe have set up small-scale clinical trials aimed at evaluating the toxicity, the antitumoral effectiveness and the immunological response in cancer patients immunized with MAGE vaccines involving either peptides, a recombinant protein or a recombinant viral vector. A total of about 380 patients have been included in these multicenter trials.
- Clinical trials
of therapeutic vaccination with MAGE tumor antigens in
cancer patients :
1 - Clinical trials with the MAGE-3.A1 peptide
Nicolas Van BAREN, Marie MARCHAND and Jérôme DEGUELDRE - Clinical trials of
therapeutic vaccination with MAGE tumor antigens in
cancer patients :
2 - Clinical trials with the MAGE-3 protein
Nicolas Van BAREN, Marie MARCHAND and Jérôme DEGUELDRE - Clinical trials of
therapeutic vaccination with MAGE tumor antigens in
cancer patients :
3 - Clinical trial with an ALVAC-MAGE virus
Nicolas Van BAREN, Marie MARCHAND and Jérôme DEGUELDRE
Summary of relevant observations and perspectives
Immunization with MAGE peptides, the MAGE-3 recombinant protein or the ALVAC recombinant viral vector, is devoid of significant toxicity. A minority of melanoma patients (about 10 to 20 %) show regression of metastatic lesions following immunization, whatever the MAGE vaccine used. About 5 to 10% of the patients show complete or partial clinical responses. Some of these lasted for several years. This frequency is far beyond the reported incidence of spontaneous regressions of melanoma metastases, estimated at 0.2-0.3%, indicating that these regressions are linked to the vaccinations. CTL responses can be detected in a minority of patients vaccinated either with peptide or ALVAC virus. The responses appear to be weak and are mainly monoclonal. The relative frequency of CTL responders versus non-responders is higher in patients who had tumor regressions (6).
Expression profiling
- Gene expression
profiling of tumor samples from vaccinated
patients
Nicolas Van BAREN and Francis BRASSEUR
Selected publications
- Marchand M., van Baren N., Weynants P., Brichard V., Dréno B., Tessier M-H., Rankin E., Parmiani G., Arienti F., Humblet Y., Bourlond A., Vanwijck R., Liénard D., Beauduin M., Dietrich P-Y., Russo V., Kerger J., Masucci G., Jäger E., De Greve J., Atzpodien J., Brasseur F., Coulie P.G., van der Bruggen P., and Boon T. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. International Journal of Cancer 1999;80:219-230
- Machiels J.P., van Baren N., Marchand M. Peptide-based Cancer Vaccines. Seminars in Oncology 2002;129:494-502.
- Coulie P. G., Karanikas V., Colau D., Lurquin C., Landry C., Marchand M., Dorval T., Brichard V. and Boon T. A monoclonal cytolytic T-lymphocyte response observed in a melanoma patient vaccinated with a tumor-specific antigenic peptide encoded by gene MAGE-3. Proceedings of the National Academy of Sciences USA 2001;98:10290-10295.
- Marchand M., Punt C.J., Aamdal S., Escudier B., Kruit W.H., Keilholz U., Hakansson L., van Baren N., Humblet Y., Mulders P., Avril M.F., Eggermont A.M., Scheibenbogen C., Uiters J., Wanders J., Delire M., Boon T., Stoter G. Immunisation of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2: a clinical report. Eur J Cancer 2003;39:70-77.
- Kruit W., van Ojik H., Brichard V., Escudier B., Dorval T., Dréno B., Patel P., van Baren N., Avril M-F., Piperno S., Khammari A., Stas M., Ritter G., Lethé B., Godelaine D., Brasseur F., Zhang Y., van der Bruggen P., Boon T., Eggermont A.and Marchand M. Phase I/II study of subcutaneous and intradermal immunization with a recombinant MAGE-3 protein in patients with detectable non-visceral metastatic melanoma. International Journal of Cancer 2005;117:596-604.
- van Baren N., Bonnet M.-C., Dreno B., Khammari A., Dorval T., Piperno-Neumann S., Lienard D., Speiser D., Marchand M., Brichard V. G., Escudier B., Negrier S., Dietrich P.-Y., Maraninchi D., Osanto S., Meyer R. G., Ritter G., Moingeon P., Tartaglia J., van der Bruggen P., Coulie P. G. and Boon T. Tumoral and immunologic response after vaccination of melanoma patients with an ALVAC virus encoding MAGE antigens recognized by T cells. Journal of Clinical Oncology 2005;23:9008-9021.