Tumoral and Immunologic Response After Vaccination of Melanoma Patients With an ALVAC Virus Encoding MAGE Antigens Recognized by T Cells
- 10 December 2005
- journal article
- clinical trial
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 23 (35), 9008-9021
- https://doi.org/10.1200/jco.2005.08.375
Abstract
Purpose: To evaluate the toxicity, antitumoral effectiveness, and immunogenicity of repeated vaccinations with ALVAC miniMAGE-1/3, a recombinant canarypox virus containing a minigene encoding antigenic peptides MAGE-3168-176and MAGE-1161-169, which are presented by HLA-A1 and B35 on tumor cells and can be recognized by cytolytic T lymphocytes (CTLs).Materials and Methods: The vaccination schedule comprised four sequential injections of the recombinant virus, followed by three booster vaccinations with the MAGE-3168-176and MAGE-1161-169peptides. The vaccines were administered, both intradermally and subcutaneously, at 3-week intervals.Results: Forty patients with advanced cancer were treated, including 37 melanoma patients. The vaccines were generally well tolerated with moderate adverse events, consisting mainly of transient inflammatory reactions at the virus injection sites. Among the 30 melanoma patients assessable for tumor response, a partial response was observed in one patient, and disease stabilization in two others. The remaining patients had progressive disease. Among the patients with stable or progressive disease, five showed evidence of tumor regression. A CTL response against the MAGE-3 vaccine antigen was detected in three of four patients with tumor regression, and in only one of 11 patients without regression.Conclusion: Repeated vaccination with ALVAC miniMAGE-1/3 is associated with tumor regression and with a detectable CTL response in a minority of melanoma patients. There is a significant correlation between tumor regression and CTL response. The contribution of vaccine-induced CTL in the tumor regression process is discussed in view of the immunologic events that could be analyzed in detail in one patient.Keywords
This publication has 35 references indexed in Scilit:
- High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigensThe Journal of Experimental Medicine, 2005
- Contrasting frequencies of antitumor and anti-vaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigenThe Journal of Experimental Medicine, 2005
- Current developments of immunotherapy in the clinicCurrent Opinion in Immunology, 2004
- Safety of intravenous administration of a canarypox virus encoding the human wild-type p53 gene in colorectal cancer patientsCancer Gene Therapy, 2003
- Cancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor LymphocytesScience, 2002
- What is a natural killer cell?Nature Immunology, 2002
- A MAGE-A1 peptide presented to cytolytic T lymphocytes by both HLA-B35 and HLA-A1 moleculesTissue Antigens, 2000
- Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes.The Journal of Experimental Medicine, 1994
- Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes.The Journal of Experimental Medicine, 1994
- A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-A1 by cytolytic T lymphocytes directed against tumor antigen MZ2-E.The Journal of Experimental Medicine, 1992