Hoon D S, Yuzuki D, Hayashida M, Morton D L
John Wayne Institute for Cancer Treatment and Research, Saint Johns' Hospital and Health Center, Santa Monica, CA 90404.
J Immunol. 1995 Jan 15;154(2):730-7.
The MAGE-1 gene was recently characterized to encode an immunogenic tumor Ag on several types of human tumors, including melanoma. This Ag is expressed in a wide variety of human tumors and not in normal cells, except testicular tissue, as assessed through specific mRNA analysis. In this study we cloned the MAGE-1 gene exon 3 region from a colon carcinoma cell line and expressed it in Escherichia coli. The recombinant MAGE-1 protein was affinity purified. By using Western blot analysis, IgG and IgM anti-MAGE-1 Abs were detected in the sera of melanoma patients. Fifty-three patients immunized with a melanoma cell vaccine (MCV) were assessed for anti-MAGE-1 IgG responses by using a MAGE-1 Ag-specific ELISA. The MCV consisted of three melanoma cell lines that expressed MAGE-1. Comparisons of anti-MAGE-1 IgG response pre-MCV treatment with 12- to 16-wk post-MCV treatment were made. Fifty-seven percent of the patients immunized with the MCV showed significant enhancement of IgG response to recombinant MAGE-1 protein. Patients who responded had no particular HLA-A or -B allele expression pattern. Melanoma patients immunized with whole cell MCV containing MAGE-1 can enhance anti-MAGE-1 IgG Abs. Recombinant MAGE-1 protein can be used to assess patient response to MAGE-1 and will be investigated as a potential cancer vaccine against a wide variety of human tumors that express MAGE-1.
MAGE-1基因最近被鉴定为在包括黑色素瘤在内的几种人类肿瘤上编码一种免疫原性肿瘤抗原。通过特异性mRNA分析评估,这种抗原在多种人类肿瘤中表达,而在正常细胞中不表达,睾丸组织除外。在本研究中,我们从结肠癌细胞系中克隆了MAGE-1基因外显子3区域,并在大肠杆菌中表达。对重组MAGE-1蛋白进行了亲和纯化。通过蛋白质印迹分析,在黑色素瘤患者血清中检测到IgG和IgM抗MAGE-1抗体。使用MAGE-1抗原特异性酶联免疫吸附测定法(ELISA)评估了53例接种黑色素瘤细胞疫苗(MCV)的患者的抗MAGE-1 IgG反应。MCV由三种表达MAGE-1的黑色素瘤细胞系组成。比较了MCV治疗前与治疗12至16周后的抗MAGE-1 IgG反应。接种MCV的患者中有57%对重组MAGE-1蛋白的IgG反应显著增强。有反应的患者没有特定的HLA-A或-B等位基因表达模式。接种含MAGE-1的全细胞MCV的黑色素瘤患者可增强抗MAGE-1 IgG抗体。重组MAGE-1蛋白可用于评估患者对MAGE-1的反应,并将作为一种潜在的癌症疫苗针对多种表达MAGE-1的人类肿瘤进行研究。