Cross-immunizing potential of tumor MAGE-A epitopes recognized by HLA-A*02:01-restricted cytotoxic T lymphocytes
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Almost all melanoma cells express at least one member of the MAGE-A antigen family, making the cytotoxic T cells (CTLs)epitopes with cross-immunizing potential in this family attractive candidates for the broad spectrum of anti-melanoma immunotherapy. In this study, four highly homologous peptides (P264: FLWGPRALA, P264I9: FLWGPRALI, P264V9:FLWGPRALV, and P264H8: FLWGPRAHA) from the MAGE-A antigens were selected by homologous alignment. All four peptides showed high binding affinity and stability to HLA-A*02:01 molecules, and could prime CTL immune responses in human PBMCs and in HLA-A*02:01/Kb transgenic mice. CTLs elicited by the four epitope peptides could cross-lyse tumor cells expressing the mutual target antigens,except MAGE-A11 which was not tested. However, CTLs induced by P264V9 and P264I9 showed the strongest target cell lysis capabilities, suggesting both peptides may represent the common CTL epitopes shared by the eight MAGE-A antigens,which could induce more potent and broad-spectrum antitumor responses in immunotherapy. [BMB Reports 2012;45(7): 408-413]
Abstract
Almost all melanoma cells express at least one member of the MAGE-A antigen family, making the cytotoxic T cells (CTLs)epitopes with cross-immunizing potential in this family attractive candidates for the broad spectrum of anti-melanoma immunotherapy. In this study, four highly homologous peptides (P264: FLWGPRALA, P264I9: FLWGPRALI, P264V9:FLWGPRALV, and P264H8: FLWGPRAHA) from the MAGE-A antigens were selected by homologous alignment. All four peptides showed high binding affinity and stability to HLA-A*02:01 molecules, and could prime CTL immune responses in human PBMCs and in HLA-A*02:01/Kb transgenic mice. CTLs elicited by the four epitope peptides could cross-lyse tumor cells expressing the mutual target antigens,except MAGE-A11 which was not tested. However, CTLs induced by P264V9 and P264I9 showed the strongest target cell lysis capabilities, suggesting both peptides may represent the common CTL epitopes shared by the eight MAGE-A antigens,which could induce more potent and broad-spectrum antitumor responses in immunotherapy. [BMB Reports 2012;45(7): 408-413]
참고문헌 (17)
- De Plaen, E., "Structure, chromosomal localization, and expression of 12 genes of the MAGE family", Immunogenetics, 40, pp.360~369 (1994)
- Jungbluth, A. A., "Expression of MAGE-antigens in normal tissues and cancer", Int. J. Cancer, 85, pp.460~465 (2000)
- Serrano, A., "Quantitative evaluation of the expression of MAGE genes in tumors by limiting dilution of cDNA libraries", Int. J. Cancer, 83, pp.664~669 (1999)
- Otte, M., "MAGE-A gene expression pattern in primary breast cancer", Cancer Res., 61, pp.6682~6687 (2001)
- Jia, Z. C., "Identification of a new MAGE-A10 antigenic peptide presented by HLA-A*0201 on tumor cells", Cancer Biol. Ther., 11, pp.395~400 (2011)
- Novellino, L., "A listing of human tumor antigens recognized by T cells: March 2004 update", Cancer Immunol. Immunother., 54, pp.187~207 (2005)
- Jia, Z. C., "Identification of two novel HLA-A*0201-restricted CTL epitopes derived from MAGE-A4", Clin. Dev. Immunol., 2010, pp.567594~ (2010)
- van der Bruggen, P., "A peptide encoded by human gene MAGE-3 and presented by HLA-A2 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3", Eur. J. Immunol., 24, pp.3038~3043 (1994)
- Tourdot, S., "A general strategy to enhance immunogenicity of low-affinity HLA-A2. 1-associated peptides: implication in the identification of cryptic tumor epitopes", Eur. J. Immunol., 30, pp.3411~3421 (2000)
- Parker, K. C., "Sequence motifs important for peptide binding to the human MHC class I molecule, HLA-A2", J. Immunol., 149, pp.3580~3587 (1992)
- Valmori, D., "Analysis of MAGE-3-specific cytolytic T lymphocytes in human leukocyte antigen-A2 melanoma patients", Cancer Res., 57, pp.735~741 (1997)
- Valmori, D., "Modulation of proteasomal activity required for the generation of a cytotoxic T lymphocyte-defined peptide derived from the tumor antigen MAGE-3", J. Exp. Med., 189, pp.895~906 (1999)
- Guillaume, B., "Two abundant proteasome subtypes that uniquely process some antigens presented by HLA class I molecules", Proc. Natl. Acad. Sci. U.S.A., 107, pp.18599~18604 (2010)
- Nijman, H. W., "Identification of peptide sequences that potentially trigger HLA-A2.1-restricted cytotoxic T lymphocytes", Eur. J. Immunol., 23, pp.1215~1219 (1993)
- Guttridge, M. G., "Identification of HLA-A*0224: implications forPCR-SSP HLA typing", Tissue Antigens, 53, pp.190~193 (1999)
- Tang, Y., "An altered peptide ligand for naive cytotoxic T lymphocyte epitope of TRP-2(180-188) enhanced immunogenicity", Cancer Immunol. Immunother., 56, pp.319~329 (2007)
- Shinohara, M. L., "T-bet-dependent expression of osteopontin contributes to T cell polarization", Proc. Natl. Acad. Sci. U.S.A., 102, pp.17101~17106 (2005)