Bellone M, Iezzi G, Martin-Fontecha A, Rivolta L, Manfredi A A, Protti M P, Freschi M, Dellabona P, Casorati G, Rugarli C
Laboratory of Tumor Immunology, San Raffaele Scientific Institute, School of Medicine, University of Milan, Italy.
J Immunol. 1997 Jan 15;158(2):783-9.
Naturally processed peptides, obtained by acid extraction of tumor cells, contain Ags able to activate specific CTL in vitro. We recently reported that the nonprofessional APC, RMA-S, expressing the B7.1 molecule (RMA-S/B7), pulsed with naturally processed peptides from the nonimmunogenic B16F1 melanoma (B16F1a.e.) primed syngenic CD8+ T cells against the tumor in vitro. Here, we show the rejection of B16F1 melanoma by C57BL/6 mice after immunization with RMA-S/B7 cells pulsed with B16F1a.e. This response is critically dependent on both CD4+ and CD8+ cells, but not on NK cells. However, only CD8+ T cells exert anti-B16F1 cytolitic activity in vitro. Moreover, RMA-S/B7 cells pulsed with B16F1a.e. can be used to prevent the growth of 24-h preestablished melanomas. These results may have important implications for the clinical use of natural peptide fractions of tumor cells as therapeutic cancer vaccines.
通过对肿瘤细胞进行酸提取获得的天然加工肽含有能够在体外激活特异性CTL的抗原。我们最近报道，表达B7.1分子的非专职抗原呈递细胞RMA-S（RMA-S/B7），用来自非免疫原性B16F1黑色素瘤（B16F1a.e.）的天然加工肽脉冲处理后，可在体外使同基因CD8+T细胞针对肿瘤致敏。在此，我们展示了用B16F1a.e.脉冲处理的RMA-S/B7细胞免疫后，C57BL/6小鼠对B16F1黑色素瘤的排斥反应。这种反应严重依赖于CD4+和CD8+细胞，但不依赖于NK细胞。然而，只有CD8+T细胞在体外发挥抗B16F1细胞溶解活性。此外，用B16F1a.e.脉冲处理的RMA-S/B7细胞可用于预防24小时前已建立的黑色素瘤的生长。这些结果可能对肿瘤细胞天然肽组分作为治疗性癌症疫苗的临床应用具有重要意义。
