Tajima Kouhei, Obata Yuichi, Tamaki Hiromi, Yoshida Masahiro, Chen Yao-Tseng, Scanlan Matthew J, Old Lloyd J, Kuwano Hiroyuki, Takahashi Takashi, Takahashi Toshitada, Mitsudomi Tetsuya
Division of Immunology, Aichi Cancer Center Research Institute, 1-1, Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan.
Lung Cancer. 2003 Oct;42(1):23-33. doi: 10.1016/s0169-5002(03)00244-7.
Cancer/testis (CT) antigens are considered promising candidates for vaccine-based immunotherapy. The aim of this study was to investigate which CT antigens should be targeted in immunotherapy of Japanese lung cancer. To determine the expression of 12 CT antigens in Japanese primary lung cancers and cell lines, a reverse-transcription polymerase chain reaction (RT-PCR) analysis was performed. Among 46 primary lung cancers, high expression rates were found for MAGE-3 (41%, 19/46), and SSX-4 (35%, 16/46). A similar pattern of CT antigen expression was observed in 29 lung cancer cell lines. The expression frequency of a certain CT antigen, namely NY-ESO-1, in Japanese cases was drastically different from that in Caucasians. Polyvalent CT antigen vaccine may be effective to increase the number of lung cancer patients eligible for cancer-specific immunotherapy. Vaccination with MAGE-3 and SSX-1 would cover 57% of all patients, with three antigens, MAGE-3, SSX-1, and MAGE-4, would cover 65%, and with four antigens, MAGE-3, SSX-1, MAGE-4 and SSX-4, would cover 70%. Simultaneous expression of two or more CT antigens was observed in 25/46 (54%) primary lung cancers and 18/29 (62%) lung cancer cell lines. Polyvalent CT antigen vaccines may be also effective to reduce a chance of emergence of antigen loss variants, thus preventing tumors from escaping from the immune system. For this purpose, vaccination with combinations of MAGE-3 with MAGE-6, SSX-4, MAGE-1 or BAGE may be effective for a quarter of Japanese lung cancer patients. In addition, in silico surveys of dbEST database were used for identification of new CT antigens. We identified a novel gene, TES101RP, expressed only in some small cell lung cancers (SCLC) and in testis, as confirmed by RT-PCR analysis.
癌/睾丸（CT）抗原被认为是基于疫苗的免疫疗法中有前景的候选物。本研究的目的是调查在日本肺癌免疫疗法中应靶向哪些CT抗原。为了确定12种CT抗原在日本原发性肺癌和细胞系中的表达情况，进行了逆转录聚合酶链反应（RT-PCR）分析。在46例原发性肺癌中，MAGE-3（41%，19/46）和SSX-4（35%，16/46）的高表达率被发现。在29个肺癌细胞系中观察到类似的CT抗原表达模式。某种CT抗原，即NY-ESO-1，在日本病例中的表达频率与白种人有很大差异。多价CT抗原疫苗可能有效地增加符合癌症特异性免疫疗法的肺癌患者数量。用MAGE-3和SSX-1进行疫苗接种将覆盖所有患者的57%，用三种抗原MAGE-3、SSX-1和MAGE-4将覆盖65%，用四种抗原MAGE-3、SSX-1、MAGE-4和SSX-4将覆盖70%。在25/46（54%）的原发性肺癌和18/29（62%）的肺癌细胞系中观察到两种或更多种CT抗原的同时表达。多价CT抗原疫苗也可能有效地减少抗原丢失变体出现的机会，从而防止肿瘤逃避免疫系统。为此，用MAGE-3与MAGE-6、SSX-4、MAGE-1或BAGE的组合进行疫苗接种可能对四分之一的日本肺癌患者有效。此外，利用dbEST数据库的电子调查来鉴定新的CT抗原。我们鉴定出一个新基因TES101RP，经RT-PCR分析证实其仅在一些小细胞肺癌（SCLC）和睾丸中表达。
