Wang Zhiqing, Zhang Yana, Mandal Arabinda, Zhang Jian, Giles Francis J, Herr John C, Lim Seah H
Division of Hematology and Oncology, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA.
Clin Cancer Res. 2004 Oct 1;10(19):6544-50. doi: 10.1158/1078-0432.CCR-04-0911.
Neoplastic cells often aberrantly express normal testicular proteins. Because these proteins have a very restricted normal tissue expression, they may be suitable targets for immunotherapy. SLLP1 is an intra-acrosomal, nonbacteriolytic, c lysozyme-like protein recently isolated from human spermatozoa. In this study, we determined whether SLLP1 is a novel cancer-testis antigen in hematologic malignancies
SLLP1 expression in hematologic tumor cells and normal tissues was determined using a combination of reverse transcription-PCR, real-time PCR, and Western blot analysis. The presence of antibodies against SLLP1 was determined by ELISA analysis.
SLLP1 was aberrantly expressed in the tumor cells from 2 of 9 acute myeloid leukemia, 3 of 11 chronic lymphocytic leukemia, 4 of 14 chronic myeloid leukemia, and 6 of 17 multiple myeloma. In contrast, they were not detected in corresponding specimens from any healthy donors. SLLP1 exhibited a very restricted normal tissue expression, being found only in testis/spermatozoa. SLLP1 was expressed in some tumor cells at a level of >25%. High titer IgG antibodies against SLLP1 were also detected in the sera of some of these patients.
SLLP1 is a novel cancer-testis antigen in hematologic malignancies and is capable of eliciting B-cell immune responses in vivo in cancer-bearing individuals. Our results, therefore, support SLLP1 as a protein target appropriate for additional in vitro study to define its suitability for immunotherapy.
肿瘤细胞常常异常表达正常睾丸蛋白。由于这些蛋白在正常组织中的表达非常局限，它们可能是免疫治疗的合适靶点。SLLP1是一种最近从人类精子中分离出的顶体内、非溶菌性、类c型溶菌酶蛋白。在本研究中，我们确定SLLP1是否为血液系统恶性肿瘤中的一种新型癌-睾丸抗原。
采用逆转录PCR、实时PCR和蛋白质印迹分析相结合的方法，检测血液系统肿瘤细胞和正常组织中SLLP1的表达。通过酶联免疫吸附测定分析确定抗SLLP1抗体的存在情况。
SLLP1在9例急性髓系白血病中的2例、11例慢性淋巴细胞白血病中的3例、14例慢性髓系白血病中的4例以及17例多发性骨髓瘤中的6例的肿瘤细胞中异常表达。相比之下，在任何健康供体的相应标本中均未检测到。SLLP1在正常组织中的表达非常局限，仅在睾丸/精子中发现。SLLP1在一些肿瘤细胞中的表达水平>25%。在其中一些患者的血清中也检测到了高滴度的抗SLLP1 IgG抗体。
SLLP1是血液系统恶性肿瘤中的一种新型癌-睾丸抗原，能够在荷瘤个体体内引发B细胞免疫反应。因此，我们的结果支持将SLLP1作为一种蛋白质靶点，进行进一步的体外研究以确定其是否适合免疫治疗。
