Characterization of novel breast carcinoma-associated BA46-derived peptides in HLA-A2.1/D(b)-beta2m transgenic mice.
The human milk fat globule membrane protein BA46 (lactadherin) is highly overexpressed in human breast tumors, making it a potential target for tumor immunotherapy. We have identified BA46-derived peptides that contain the motif recognized by the MHC class I molecule HLA-A2.1 and that are processed and presented by human breast carcinoma cells. In mice lacking normal class I molecules but expressing an HLA-A2.1/D(b)-beta2 microglobulin single chain (HHD mice), three peptides elicited specific CTL activity. Two of these peptides also stimulated cytotoxic activity in peripheral blood lymphocytes from HLA-A2.1-positive breast carcinoma patients. Adoptive transfer of HHD-derived bulk CTLs to nude mice bearing human breast carcinoma transplants reduced tumor growth. These peptides therefore represent naturally processed BA46-derived CTL epitopes that can be used in peptide-based antitumor vaccines.
Carmon
Lior
L
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Bobilev-Priel
Irene
I
Brenner
Baruch
B
Bobilev
Dimitry
D
Paz
Adrian
A
Bar-Haim
Erez
E
Tirosh
Boaz
B
Klein
Tirza
T
Fridkin
Mati
M
Lemonnier
Francois
F
Tzehoval
Esther
E
Eisenbach
Lea
L
D019264:Adoptive Transfer; D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002457:Cell Extracts / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D012334:RNA, Neoplasm / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000235:genetics*
D000954:Antigens, Surface; D002457:Cell Extracts; D000939:Epitopes; D015789:HLA-A2 Antigen; C098942:MFGE8 protein, human; C490919:Mfge8 protein, mouse; D008894:Milk Proteins; D009363:Neoplasm Proteins; D010455:Peptides; D012334:RNA, Neoplasm; D001613:beta 2-Microglobulin