Atanackovic Djordje, Arfsten Julia, Cao Yanran, Gnjatic Sacha, Schnieders Frank, Bartels Katrin, Schilling Georgia, Faltz Christiane, Wolschke Christine, Dierlamm Judith, Ritter Gerd, Eiermann Thomas, Hossfeld Dieter Kurt, Zander Axel R, Jungbluth Achim A, Old Lloyd J, Bokemeyer Carsten, Kröger Nicolaus
Department of Oncology/Hematology, Institute for Biochemistry and Molecular Biology, University Medical Center Hamburg-Eppendorf, Germany.
Blood. 2007 Feb 1;109(3):1103-12. doi: 10.1182/blood-2006-04-014480. Epub 2006 Oct 5.
Immunotherapies using cancer-testis (CT) antigens as targets represent a potentially useful treatment in patients with multiple myeloma (MM) who commonly show recurrent disease following chemotherapy. We analyzed the expression of 11 CT antigens in bone marrow samples from patients with MM (n=55) and healthy donors (n=32) using reverse transcriptase-polymerase chain reaction (RT-PCR). CT antigens were frequently expressed in MM with 56% (MAGEC2), 55% (MAGEA3), 35% (SSX1), 20% (SSX4, SSX5), 16% (SSX2), 15% (BAGE), 7% (NY-ESO-1), and 6% (ADAM2, LIPI) expressing the given antigen. Importantly, CT antigens were not expressed in healthy bone marrow. Analyzing patients with MM (n=66) for antibody responses against MAGEA3, SSX2, and NY-ESO-1, we found strong antibody responses against CT antigens preferentially in patients who had received allogeneic stem cell transplantation (alloSCT). Antibody responses against NY-ESO-1 correlated with NY-ESO-1-specific CD4+ and CD8+ T-cell responses against peptide NY-ESO-1(51-62) and CD4+ responses against NY-ESO-1(121-140) in 1 of these patients. These allogeneic immune responses were not detectable in pretransplantation samples and in the patients' stem cell donors, indicating that CT antigens might indeed represent natural targets for graft-versus-myeloma effects. Immune responses induced by alloSCT could be boosted by active CT antigen-specific immunotherapy, which might help to achieve long-lasting remissions in patients with MM.
以癌-睾丸（CT）抗原为靶点的免疫疗法对多发性骨髓瘤（MM）患者可能是一种有效的治疗方法，这类患者在化疗后常出现疾病复发。我们采用逆转录聚合酶链反应（RT-PCR）分析了55例MM患者和32例健康供者骨髓样本中11种CT抗原的表达情况。CT抗原在MM中频繁表达，其中56%（MAGEC2）、55%（MAGEA3）、35%（SSX1）、20%（SSX4、SSX5）、16%（SSX2）、15%（BAGE）、7%（NY-ESO-1）以及6%（ADAM2、LIPI）表达相应抗原。重要的是，健康骨髓中未检测到CT抗原的表达。在66例MM患者中分析针对MAGEA3、SSX2和NY-ESO-1的抗体反应，我们发现接受异基因干细胞移植（alloSCT）的患者对CT抗原的抗体反应更强。在其中1例患者中，针对NY-ESO-1的抗体反应与针对肽NY-ESO-1(51-62)的NY-ESO-1特异性CD4+和CD8+ T细胞反应以及针对NY-ESO-1(121-140)的CD4+反应相关。这些异基因免疫反应在移植前样本和患者的干细胞供者中未检测到，表明CT抗原可能确实是移植物抗骨髓瘤效应的天然靶点。alloSCT诱导的免疫反应可通过主动的CT抗原特异性免疫疗法增强，这可能有助于MM患者实现长期缓解。
