Hu X, Chakraborty N G, Sporn J R, Kurtzman S H, Ergin M T, Mukherji B
Department of Medicine, University of Connecticut School of Medicine, Farmington 06030, USA.
Cancer Res. 1996 Jun 1;56(11):2479-83.
Identification of human melanoma-associated peptide antigens for CTLs has opened unprecedented opportunities for active specific immunotherapy for melanoma with synthetic peptide. We have shown that immunization with a MAGE-1 gene encoded nonapeptide (EADPT-GHSY)-pulsed autologous antigen presenting cell-based vaccine induces autologous melanoma-reactive and peptide-specific CTL response, in situ, at the vaccination site and at distant tumor deposits in patients who are HLA-A1+ and whose melanoma cells express the MAGE-1 mRNA. Here, we show that such immunization is also capable of increasing the frequency of autologous melanoma-reactive CTL precursors in the circulation. We further show that in vitro stimulation of the postimmunization peripheral blood lymphocytes with the MAGE-1 nonapeptide-loaded antigen presenting cell and interleukin-2 leads to significant expansion of peptide-specific and autologous melanoma-reactive CTL response.
鉴定用于细胞毒性T淋巴细胞(CTL)的人类黑色素瘤相关肽抗原,为用合成肽对黑色素瘤进行主动特异性免疫治疗带来了前所未有的机遇。我们已经表明,用MAGE-1基因编码的九肽(EADPT-GHSY)脉冲处理的基于自体抗原呈递细胞的疫苗进行免疫,可在接种部位以及HLA-A1阳性且黑色素瘤细胞表达MAGE-1 mRNA的患者的远处肿瘤沉积物中,原位诱导自体黑色素瘤反应性和肽特异性CTL反应。在此,我们表明这种免疫还能够增加循环中自体黑色素瘤反应性CTL前体的频率。我们进一步表明,用负载MAGE-1九肽的抗原呈递细胞和白细胞介素-2在体外刺激免疫后的外周血淋巴细胞,会导致肽特异性和自体黑色素瘤反应性CTL反应显著扩增。