1. A peptide encoded by human gene MAGE-3 and presented by HLA-A2 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3
P van der Bruggen, J Bastin, T Gajewski, P G Coulie, P Boël, C De Smet, C Traversari, A Townsend, T Boon Eur J Immunol. 1994 Dec;24(12):3038-43. doi: 10.1002/eji.1830241218.
The human MAGE-3 gene is expressed in many tumors of several histological types but it is silent in normal tissues, with the exception of testis. Antigens encoded by MAGE-3 may, therefore, be useful targets for specific anti-tumor immunization of cancer patients. We reported previously that MAGE-3 codes for an antigenic peptide recognized on a melanoma cell line by autologous cytolytic T lymphocytes (CTL) restricted by HLA-A1. Here we report that the MAGE-3 gene also codes for another antigenic peptide that is recognized by CTL restricted by HLA-A2. MAGE-3 peptides bearing consensus anchor residues for HLA-A2 were synthesized and tested for binding. T lymphocytes from normal individuals were stimulated with autologous irradiated lymphoblasts pulsed with each of three peptides that showed strong binding to HLA-A2. Peptide FLWGPRALV was able to induce CTL. We obtained CTL clones that recognized not only HLA-A2 cells pulsed with this peptide but also HLA-A2 tumor cell lines expressing the MAGE-3 gene. The proportion of melanoma tumors expressing this antigen should be approximately 32% in Caucasian populations, since 49% of individuals carry the HLA-A2 allele and 65% of melanomas express MAGE-3.
2. Identification of a MAGE-1 peptide recognized by cytolytic T lymphocytes on HLA-B*5701 tumors
V Corbière, H Nicolay, V Russo, V Stroobant, V Brichard, T Boon, P van der Bruggen Tissue Antigens. 2004 May;63(5):453-7. doi: 10.1111/j.0001-2815.2004.00203.x.
"Cancer germline" genes such as those of the MAGE family are expressed in many tumors and in male germline cells but are silent in normal tissues. They encode shared tumor-specific antigens that have been used in therapeutic vaccination trials of cancer patients. We report the identification of a new MAGE-1-encoded peptide that is recognized by a cytolytic T-lymphocyte (CTL) clone on human leukocyte antigen (HLA)-B*5701. The sequence of the peptide, corresponding to position 102-112 of the MAGE-1 protein sequence, is ITKKVADLVGF. When tumor cells expressing MAGE-1 were transfected with HLA-B*5701, they were lyzed by the CTL clone, indicating that the peptide is processed in tumor cells and can, therefore, be used as a target for anti-tumoral vaccination.
3. A new MAGE-4 antigenic peptide recognized by cytolytic T lymphocytes on HLA-A24 carcinoma cells
Sabrina Ottaviani, Didier Colau, Pierre van der Bruggen Cancer Immunol Immunother. 2006 Jul;55(7):867-72. doi: 10.1007/s00262-005-0053-2. Epub 2005 Sep 3.
"Cancer-germline" genes such as those of the MAGE family are expressed in many tumors and in male germline cells, but are silent in other normal tissues. They encode tumor specific antigens that are used in cancer immunotherapy trials. MAGE-4 antigens represent promising targets for cancer immunotherapy because gene MAGE-4 is expressed in more than 50% of carcinomas of the esophagus, lung, bladder, and head and neck. To identify new MAGE-4 antigenic peptides, we have folded HLA-A*2402 soluble molecules with candidate peptide NYKRCFPVI, which corresponds to amino acids 143 to151 of the MAGE-4 protein. A24/MAGE-4 multimers were used to isolate a cytolytic T cell clone that recognized the MAGE-4 peptide from the blood cells of a donor without cancer. This clone lysed specifically A24 carcinoma cells expressing MAGE-4. The antigenic peptide is processed more efficiently in tumor cells pre-treated with IFN-gamma. This MAGE-4 peptide could represent an interesting target for immunotherapy because it is presented by HLA-A24 molecules, which are widely expressed in different ethnic groups.
