Co-administration of GP96 and Her2/neu DNA vaccine in a Her2 breast cancer model.
Heat-shock proteins have biochemical and immunological roles in chaperoning/signaling and activation of innate and adaptive immune responses, respectively. Their effect on the immune response is due to a phenomenon known as cross-priming of antigen, in which exogenous antigens are presented via MHC class I by antigen presenting cells. GP96 exerts adjuvant activity with some viral and bacterial antigens when applied in the form of a DNA vaccine. In this study, animals with Her2-expressing tumors were vaccinated by co-administration of GP96+ Her2/neu DNA vaccines. Analyses of the immune response, 2 weeks after the last immunization revealed decreased CD4+ CD25+ Foxp3+ naturally occurring regulatory T cells (Tregs) at the tumor site and increased IFN-γ/IL-4 level. Nevertheless, the graph of tumor size demonstrated a bi-phasic pattern in which partial control of tumor progression initially occurred, but finally its effectiveness was inversely affected by tumor size.
Pakravan
Nafiseh
N
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Ale-Ahmad Avenue, P.O. Box: 14115-331, Tehran, Iran.
Langroudi
Ladan
L
Hajimoradi
Monire
M
Hassan
Zuhair Mohammad
ZM
D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology*
D019496:Cancer Vaccines; D051858:Forkhead Transcription Factors; D007371:Interferon-gamma; D053645:Interleukin-2 Receptor alpha Subunit; D015847:Interleukin-4; D008562:Membrane Glycoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA; C498833:Foxp3 protein, mouse; C053387:endoplasmin; C524056:Erbb2 protein, mouse