Pre-Existing Immunity to Tyrosinase-Related Protein (TRP)-2, a New TRP-2 Isoform, and the NY-ESO-1 Melanoma Antigen in a Patient with a Dramatic Response to Immunotherapy
Pre-Existing Immunity to Tyrosinase-Related Protein (TRP)-2, a New TRP-2 Isoform, and the NY-ESO-1 Melanoma Antigen in a Patient with a Dramatic Response to Immunotherapy
复制标题
对免疫治疗有显着反应的患者对酪氨酸酶相关蛋白 (TRP)-2、一种新的 TRP-2 异构体和 NY-ESO-1 黑色素瘤抗原已有免疫力
作者：
H. Khong;S. Rosenberg
我们已经进行了一个详细的分析识别黑色素瘤抗原的肿瘤浸润淋巴细胞（TIL）1790，从一个病人谁经历了戏剧性的肿瘤消退后，免疫肽从gp 100，MART-1，和酪氨酸酶抗原。发现该TIL识别酪氨酸酶相关蛋白（TRP）-2（克隆MR 7）和NY-ESO-1（克隆M8）中的HLA-A2限制性CTL表位。这些表位与先前鉴定的九肽TRP-2：180-188和重叠NY-ESO-1肽相同，通过使用来自体外刺激的淋巴细胞获得。我们还克隆了一个以前未知的TRP-2 mRNA亚型（TRP-2- 6 b），其中包含两个新的外显子，从TRP-2 mRNA的外显子6和7之间的第六内含子选择性剪接。同种型编码由TIL克隆MB 4识别的HLA-A2限制性抗原表位。治疗前获得的患者PBMC的免疫学分析显示存在针对NY-ESO-1和TRP-2 Ag的高反应性，但不存在针对用于免疫的Ag的高反应性。由于针对这些Ag的免疫应答不太明显，因此NY-ESO-1、TRP-2和TRP-2- 6 b可能在CTL介导的肿瘤破坏的产生中具有重要性，并且可能在该患者中观察到的显著肿瘤消退中发挥作用。
We have performed a detailed analysis of the recognition of melanoma Ags by the tumor-infiltrating lymphocytes (TIL) 1790, isolated from a patient who experienced a dramatic tumor regression following immunization with peptides from the gp100, MART-1, and tyrosinase Ags. This TIL was found to recognize HLA-A2-restricted CTL epitopes in tyrosinase-related protein (TRP)-2 (clone MR7) and NY-ESO-1 (clone M8). These epitopes were the same as the previously identified nonapeptide TRP-2: 180–188, and the overlapping NY-ESO-1 peptides, obtained by using lymphocytes from in vitro stimulation. We also cloned a previously unknown TRP-2 mRNA isoform (TRP-2-6b) that contained two novel exons alternatively spliced from the sixth intron between exons 6 and 7 of TRP-2 mRNA. The isoform encoded an HLA-A2-restricted antigenic epitope recognized by TIL clone MB4. An immunologic analysis of the patient’s PBMC obtained before treatment showed the presence of high reactivity against NY-ESO-1 and both TRP-2 Ags, but not the Ags used for immunization. Because immune response against these Ags was less pronounced, it is possible that NY-ESO-1, TRP-2, and TRP-2-6b may be of importance in the generation of CTL-mediated tumor destruction and may have played a role in the dramatic tumor regression seen in this patient.
影响因子：
11.2
作者：
M. Parkhurst;E. Fitzgerald;S. Southwood;Alessandro Sette;Steven A. Rosenberg;Yutaka Kawakami
通讯作者：
M. Parkhurst;E. Fitzgerald;S. Southwood;Alessandro Sette;Steven A. Rosenberg;Yutaka Kawakami