Human Mena protein, a serex-defined antigen overexpressed in breast cancer eliciting both humoral and CD8+ T-cell immune response.
Screening of a cDNA expression library from a primary breast tumor with the autologous patient serum led to the isolation of 6 cDNA clones corresponding to 3 different genes, including a novel gene that maps to chromosome 1 and encodes the human homologue of mouse Mena (hMena, cDNA clone RMNY-BR-55), a protein of the Ena/VASP family involved in the regulation of cell motility and adhesion. A cancer-restricted antibody response against hMena was demonstrated, since 18/93 cancer patient sera, the majority (10/52) from breast cancer, showed anti-hMena-specific IgG, while no antibodies were present in healthy donors. When hMena protein expression was analyzed by Western blot and immunohistochemistry, the antigen was overexpressed in the majority of breast cancer cell lines and in 75% of primary breast tumor lesions evaluated. Furthermore, when HLA-A2-restricted peptides from the hMena sequence were used to stimulate CD8+ T cells, an hMena-specific response was found in 9 out of 12 HLA-A2+ breast cancer patients. In 4 patients, this cell-mediated immune response was concomitant with antibody response to hMena. Furthermore, an hMena-specific T-cell line was established from an HLA-A2+ breast cancer patient whose primary tumor lesion overexpressed the hMena protein. The present findings highlight the emerging role that overexpression of cytoskeleton regulatory components may have in the induction of a specific antitumor immune response.
Di Modugno
Francesca
F
Laboratory of Experimental Chemotherapy, Regina Elena Cancer Institute, Rome, Italy.
Bronzi
Giovanna
G
Scanlan
Matthew J
MJ
Del Bello
Duilia
D
Cascioli
Simona
S
Venturo
Irene
I
Botti
Claudio
C
Nicotra
Maria Rita
MR
Mottolese
Marcella
M
Natali
Pier Giorgio
PG
Santoni
Angela
A
Jager
Elke
E
Nisticò
Paola
P
D000912:Antibodies, Neoplasm / Q000276:immunology*; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000276:immunology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D044584:Carcinoma, Ductal / Q000276:immunology; D018275:Carcinoma, Lobular / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D003598:Cytoskeletal Proteins; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D008840:Microfilament Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C102176:Enah protein, mouse; D015789:HLA-A2 Antigen; D008840:Microfilament Proteins