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Analysis of MAGE-3-specific cytolytic T lymphocytes in human leukocyte antigen-A2 melanoma patients

Analysis of MAGE-3-specific cytolytic T lymphocytes in human leukocyte antigen-A2 melanoma patients. Valmori, Danila; Lienard, Danielle; Waanders, Gary; Rimolodi, Donata; Cerottini, Jean-Charles; Romero, Pedro (Ludwig Inst. for Cancer Res., Univ. of Lausanne, Lausanne 1011, Switz.). Cancer Research, 57(4), 735-741 (English) 1997 American Association for Cancer Research. CODEN: CNREA8. ISSN: 0008-5472. DOCUMENT TYPE: Journal CA Section: 15 (Immunochemistry) The MAGE-3 gene is a member of a multigene family that is selectively expressed by subsets of different human tumor types, including malignant melanoma, but not by normal tissues except for testis and placenta. A cytolytic T lymphocyte (CTL)-defined MAGE-3 antigen, corresponding to the MAGE-3 peptide 271-279 assocd. with the human leukocyte antigen (HLA)-A2 mol., has been recently identified using T lymphocytes from a normal individual stimulated in vitro with peptide-pulsed autologous antigen-presenting cells. Because MAGE-3 is expressed in 76% of metastatic melanomas, the HLA-A2-restricted MAGE-3 antigen should be expressed by approx. 37% of Caucasians bearing a metastatic melanoma tumor, thus representing an attractive candidate for the elicitation of specific CTL immune responses in vivo. In this study, we detd. the proportion of HLA-A2+ melanoma patients displaying detectable MAGE-3 peptide 271-279-specific CTL precursors in peripheral blood. Peptide-specific CTL populations were obtained from at least 4 of 11 HLA-A2+ patients.Several substances like 160295-81-8 may be metioned in this study. Peptide-specific CTL lines derived from these populations readily lysed HLA-A2-pos. target cells that were pulsed with MAGE-3 peptide 271-279 at nanomolar concns. yet were unable to recognize (as assessed by cytolysis and cytokine prodn.) MAGE-3-expressing autologous or allogeneic HLA-A2-pos. melanoma lines. Similarly, the CTL lines failed to recognize MAGE-3-neg. HLA-A2-pos. tumor lines after transfection with the MAGE-3 gene, although they were able to recognize COS-7 cells transfected with MAGE-3. In contrast, HLA-A1-pos. melanoma lines transfected with MAGE-3 were efficiently recognized by CTL lines directed against the MAGE-3 peptide 168-176, a known HLA-A1-restricted CTL epitope. These results suggest that the expression level of the MAGE-3 peptide 271-279, unlike that of MAGE-3 peptide 168-176, in melanomas may be too low to allow efficient recognition by specific CTLs. Thus, it appears that despite the presence of CTL precursors against MAGE-3 peptide 271-279 in some HLA-A2+ melanoma patients, the usefulness of this peptide for specific immunotherapy of melanoma may be limited. .