Rivoltini L, Loftus D J, Squarcina P, Castelli C, Rini F, Arienti F, Belli F, Marincola F M, Geisler C, Borsatti A, Appella E, Parmiani G
Istituto Nazionale dei Tumori, Milano, Italy.
Crit Rev Immunol. 1998;18(1-2):55-63. doi: 10.1615/critrevimmunol.v18.i1-2.70.
Several T cell-recognized epitopes presented by melanoma cells have been identified recently. Despite the large array of epitopes potentially available for clinical use, it is still unclear which of these antigens could be effective in mediating anti-tumor responses when used as a vaccine. Preliminary studies showed that immunization of melanoma patients with epitopes derived from proteins of the MAGE family may result in significant clinical regressions. However, no sign of systemic immunization could be observed in peripheral blood of treated patients. Conversely, significant immunization (detected as increased antigen-specific CTL activity in peripheral blood) was obtained by vaccinating HLA-A2.1+ melanoma patients with the immunodominant epitope (residues 27-35) of the differentiation antigen MART-1, but this immunization was not accompanied by a significant clinical response. To implement immunotherapeuties capable of significantly impacting disease outcome, it is necessary to identify the potential mechanisms responsible for the failure of some antigens to mediate significant anti-tumor responses in vivo. In the case of the MART-1(27-35) epitope, we hypothesize that one of these mechanisms may be related to the existence of natural analogs of this peptide in other human normal proteins.
最近已经鉴定出黑色素瘤细胞呈递的几种T细胞识别表位。尽管有大量潜在可用于临床的表位，但仍不清楚这些抗原中哪些用作疫苗时能有效介导抗肿瘤反应。初步研究表明，用源自MAGE家族蛋白的表位免疫黑色素瘤患者可能会导致显著的临床缓解。然而，在接受治疗患者的外周血中未观察到全身免疫的迹象。相反，通过用分化抗原MART-1的免疫显性表位（第27-35位氨基酸残基）对HLA-A2.1+黑色素瘤患者进行疫苗接种，获得了显著的免疫反应（在外周血中检测为抗原特异性CTL活性增加），但这种免疫反应并未伴随显著的临床反应。为了实施能够显著影响疾病转归的免疫疗法，有必要确定某些抗原在体内无法介导显著抗肿瘤反应的潜在机制。就MART-1(27-35)表位而言，我们推测这些机制之一可能与该肽在其他人类正常蛋白中的天然类似物的存在有关。
