Her-2 DNA versus cell vaccine: immunogenicity and anti-tumor activity.
Direct comparison and ranking of vaccine formulations in pre-clinical studies will expedite the identification of cancer vaccines for clinical trials. Two human ErbB-2 (Her-2) vaccines, naked DNA and whole cell vaccine, were tested side-by-side in wild type and Her-2 transgenic mice. Both vaccines can induce humoral and cellular immunity to the entire repertoire of Her-2 epitopes. Mice were electro-vaccinated i.m. with a mixture of pGM-CSF and pE2TM, the latter encodes Her-2 extracellular and transmembrane domains. Alternatively, mice were injected i.p. with human ovarian cancer SKOV3 cells that have amplified Her-2. In wild type mice, comparable levels of Her-2 antibodies (Ab) were induced by these two vaccines. However, T cell immunity and protection against Her-2(+) tumors were superior in DNA vaccinated mice. In BALB Her-2 transgenic (Tg) mice, which were tolerant to Her-2, DNA and cell vaccines were administered after regulatory T cells (Treg) were removed by anti-CD25 mAb. Again, comparable levels of Her-2 Ab were induced, but DNA vaccines rendered greater anti-tumor activity. In B6xDR3 Her-2 Tg mice that expressed the autoimmune prone HLA-DR3 allele, higher levels of Her-2 Ab were induced by SKOV3 cell than by Her-2 DNA. But anti-tumor activity was still more profound in DNA vaccinated mice. Therefore, Her-2 DNA vaccine induced greater anti-tumor immunity than cell vaccine, whether mice were tolerant to Her-2 or susceptible to autoimmunity. Through such side-by-side comparisons in appropriate pre-clinical test systems, the more effective vaccine formulations will emerge as candidates for clinical trials.
Whittington
Paula J
PJ
Department of Immunology and Microbiology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
Radkevich-Brown
Olga
O
Jacob
Jennifer B
JB
Jones
Richard F
RF
Weise
Amy M
AM
Wei
Wei-Zen
WZ
D000818:Animals; D017951:Antigen Presentation; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000276:immunology / Q000637:transplantation; D005260:Female; D018734:Genes, erbB-2; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D059805:HLA-DR alpha-Chains; D059811:HLA-DRB1 Chains; D006801:Humans; D007111:Immunity, Cellular; D016233:Immunotherapy, Active / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000473:pathology; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D019496:Cancer Vaccines; D006023:Glycoproteins; D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; D059811:HLA-DRB1 Chains; D007371:Interferon-gamma; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA; C483804:Erbb2 protein, rat