Tumoral and immunologic response after vaccination of melanoma patients with an ALVAC virus encoding MAGE antigens recognized by T cells.
OBJECTIVE
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-3(168-176) and MAGE-1(161-169), which are presented by HLA-A1 and B35 on tumor cells and can be recognized by cytolytic T lymphocytes (CTLs).


METHODS
The vaccination schedule comprised four sequential injections of the recombinant virus, followed by three booster vaccinations with the MAGE-3(168-176) and MAGE-1(161-169) peptides. 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.


CONCLUSIONS
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.
van Baren
Nicolas
N
Ludwig Institute for Cancer Research, 74 avenue Hippocrate, UCL7459, B-1200 Brussels, Belgium; e-mail: nicolas.vanbaren@bru.licr.org.
Bonnet
Marie-Claude
MC
Dréno
Brigitte
B
Khammari
Amir
A
Dorval
Thierry
T
Piperno-Neumann
Sophie
S
Liénard
Danielle
D
Speiser
Daniel
D
Marchand
Marie
M
Brichard
Vincent G
VG
Escudier
Bernard
B
Négrier
Sylvie
S
Dietrich
Pierre-Yves
PY
Maraninchi
Dominique
D
Osanto
Susanne
S
Meyer
Ralf G
RG
Ritter
Gerd
G
Moingeon
Philippe
P
Tartaglia
Jim
J
van der Bruggen
Pierre
P
Coulie
Pierre G
PG
Boon
Thierry
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000276:immunology; D028121:Canarypox virus / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome; D014765:Viral Vaccines / Q000276:immunology*
C078788:ALVAC vaccine; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D014765:Viral Vaccines