Challenge with mammary tumor cells expressing MHC class II and CD80 prevents the development of spontaneously arising tumors in MMTV-neu transgenic mice.
The HER-2/Neu oncogene has been implicated in human and mouse breast cancer. Indeed, transgenic MMTV-neu mice expressing this oncogene from the mammary tumor virus long terminal repeat develop spontaneous mammary tumors and die within 1 year of life. We have expressed the class II transactivator (CIITA) and/or the costimulatory molecule CD80 (B7.1) in a mammary carcinoma cell line (MCNeuA) derived from these mice. Class II transactivator directs the expression of MHC class II and the machinery for antigen processing and presentation by this pathway. When injected into MMTV-neu mice, tumor cells expressing CD80 or CD80 and CIITA, were rejected completely. In addition, following the rejection of dual expressing cells, 75% of the mice were protected against the development of subsequent spontaneous tumors. Cells expressing only CD80 or CIITA were not as effective as antitumor vaccines in preventing the development of spontaneous tumors. Thus, converting cancer cells into antigen presenting cells could represent an effective immunotherapy for breast cancer.
Jabrane-Ferrat
N
N
Institut de Sciences et Technologies du Medicament de Toulouse, CNRS-Pierre Fabre, Toulouse, France.
Campbell
M J
MJ
Esserman
L J
LJ
Peterlin
B M
BM
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008214:Lymphocytes / Q000276:immunology; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D018122:B7-1 Antigen; D009687:Nuclear Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; C083728:MHC class II transactivator protein