Delayed tumor onset and reduced tumor growth progression after immunization with a Her-2/neu multi-peptide vaccine and IL-12 in c-neu transgenic mice.
Passive immunotherapy with monoclonal antibodies is a routinely performed but cost intensive treatment against certain cancers. Induction of humoral anti-tumor responses by active peptide immunization has therefore become a favorable treatment concept. We have recently identified three peptides representing B-cell epitopes of the extracellular domain of Her-2/neu each of them inducing Her-2/neu specific immune responses with anti-tumor activity in vitro. The present study was performed to evaluate the in vivo protective capacity of a combined vaccination with these three peptides in FVB/N transgenic mice spontaneously developing c-neu overexpressing breast cancers. The three Her-2/neu peptides coupled to tetanus toxoid were administered with or without addition of recombinant IL-12. At the time all untreated mice had developed tumors about 40% of peptide-immunized mice and nearly 60% of mice immunized with the peptide vaccine co-applied with IL-12 remained tumor free. Moreover, co-administration of IL-12 had a significant impact on the retardation of tumor progression. The enhanced anti-tumor efficacy of the vaccine by IL-12 was associated with a Th1 biased immune response as demonstrated by an increased IFN-gamma production in vitro and elevated Her-2-specific IgG levels. Our findings clearly demonstrate that this multi-peptide vaccine is effective in tumor prevention and support its use against minimal disease, drug-resistant tumors or even for prophylaxis against cancers overexpressing Her-2/neu.
Wagner
Stefan
S
Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.
Jasinska
Joanna
J
Breiteneder
Heimo
H
Kundi
Michael
M
Pehamberger
Hubert
H
Scheiner
Otto
O
Zielinski
Christoph C
CC
Wiedermann
Ursula
U
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000378:metabolism; D000917:Antibody Formation; D000918:Antibody Specificity; D019496:Cancer Vaccines / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000494:pharmacology* / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D022223:Vaccines, Subunit / Q000494:pharmacology* / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000906:Antibodies; D019496:Cancer Vaccines; D018985:Epitopes, B-Lymphocyte; D006023:Glycoproteins; D007074:Immunoglobulin G; D007371:Interferon-gamma; D018664:Interleukin-12; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; C508053:ERBB2 protein, human; C483804:Erbb2 protein, rat