CD4+ T cell-mediated HER-2/neu-specific tumor rejection in the absence of B cells.
HER-2/neu (HER-2) is a cell surface proto-oncogene that is often overexpressed in carcinomas. Passive administration of anti-HER-2 antibodies in breast cancer patients has achieved promising results, but less is known about the role of antibodies in active immunization. We asked whether B cells/antibodies are needed for tumor immunity induced by plasmid (HER-2 and GM-CSF) immunization. HER-2 specific tumor immunity relied completely on both CD4+ and CD8+ T cells. IFN-gamma, and to a lesser extent IL-4, seemed to be crucial cytokines during tumor rejection. Protection was associated with production of anti-HER-2 IgG antibodies in B cell competent mice. After immunization, however, B cell-deficient mice rejected HER-2-expressing tumors as efficiently as control littermates. We conclude that T cells are the main effector cells in DNA vaccine induced immunity against HER-2 and that anti HER-2 antibodies are not necessary to elicit a protective anti tumor immune response in this model.
Lindencrona
Jan Alvar
JA
Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.
Preiss
Susanne
S
Kammertoens
Thomas
T
Schüler
Thomas
T
Piechocki
Marie
M
Wei
Wei-Zen
WZ
Seliger
Barbara
B
Blankenstein
Thomas
T
Kiessling
Rolf
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001402:B-Lymphocytes / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D008212:Lymphocyte Depletion; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000276:immunology; D015996:Survival Rate; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage*
D000911:Antibodies, Monoclonal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA; C000715470:MAS1 protein, human