de Carvalho Fabricio, Vettore Andre L, Inaoka Riguel J, Karia Bruno, Andrade Valéria C C, Gnjatic Sacha, Jungbluth Achim A, Colleoni Gisele W B
Disciplina de Hematologia e Hemoterapia, Universidade Federal de São Paulo, São Paulo, Brazil.
Cancer Immun. 2011 Jan 20;11:1.
Due to the high homology between the LAGE-1 and NY-ESO-1 proteins, we hypothesized that an anti-NY-ESO-1 vaccine might elicit LAGE-1 immunity and hence may be effective in multiple myeloma (MM) patients with LAGE-1-positive/NY-ESO-1-negative tumors. Therefore, we set out to evaluate LAGE-1 and NY-ESO-1 mRNA and protein expression in MM patients in a bid to evaluate possible benefits of their homology for immunotherapy. LAGE-1 (a and b isoforms) and NY-ESO-1 mRNA expression was studied in 18 normal tissues and 50 bone marrow MM samples by RT-PCR. LAGE-1 and NY-ESO-1 protein expression was analyzed by immunohistochemistry (IHC) in 27 MM specimens using mAbs 219-510-23 and E978. Spontaneous serological immune response against both antigens was analyzed by ELISA in sera from 33 MM patients. LAGE-1 (a and b isoforms) was positive in 42% and NY-ESO-1 in 26% of the MM samples analyzed by RT-PCR. Both genes were found to be expressed in 18% of the cases, while at least one of the genes was found to be expressed in 50% of the cases. In LAGE-1 positive samples, 81% were positive for LAGE-1a and 19% were positive for both LAGE-1a and -1b. LAGE-1 and NY-ESO-1 protein expression could only be detected in two cases by IHC and there was a clear strong spontaneous antibody response to LAGE-1 and NY-ESO-1 in only one MM patient. In conclusion, LAGE-1a and NY-ESO-1 homology cannot be easily exploited in an anti-NY-ESO-1 vaccine given the low frequency of protein expression detected by IHC or serum analysis.
由于LAGE-1和NY-ESO-1蛋白之间具有高度同源性，我们推测抗NY-ESO-1疫苗可能引发LAGE-1免疫，因此可能对患有LAGE-1阳性/NY-ESO-1阴性肿瘤的多发性骨髓瘤（MM）患者有效。因此，我们着手评估MM患者中LAGE-1和NY-ESO-1的mRNA和蛋白表达，以评估它们的同源性对免疫治疗的潜在益处。通过逆转录聚合酶链反应（RT-PCR）研究了18个正常组织和50份骨髓MM样本中LAGE-1（a和b亚型）和NY-ESO-1的mRNA表达。使用单克隆抗体219-510-23和E978，通过免疫组织化学（IHC）分析了27份MM标本中LAGE-1和NY-ESO-1的蛋白表达。通过酶联免疫吸附测定（ELISA）分析了33例MM患者血清中针对这两种抗原的自发血清学免疫反应。通过RT-PCR分析，MM样本中LAGE-1（a和b亚型）阳性率为42%，NY-ESO-1阳性率为26%。在18%的病例中发现这两个基因均表达，而在50%的病例中发现至少有一个基因表达。在LAGE-1阳性样本中，81%为LAGE-1a阳性，19%为LAGE-1a和-1b均阳性。通过IHC仅在两例中检测到LAGE-1和NY-ESO-1蛋白表达，并且仅在一名MM患者中观察到针对LAGE-1和NY-ESO-1的明显强烈自发抗体反应。总之，鉴于通过IHC或血清分析检测到的蛋白表达频率较低，抗NY-ESO-1疫苗难以轻易利用LAGE-1a和NY-ESO-1的同源性。
