Bei R, Masuelli L, Moriconi E, Visco V, Moretti A, Kraus M H, Muraro R
Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.
Oncogene. 1999 Feb 11;18(6):1267-75. doi: 10.1038/sj.onc.1202442.
Employing NIH3T3 transfectants with individual human ErbB receptor coding sequences as recombinant antigen sources, we detected by immunoblot analysis specific immunoreactivity against all four ErbB receptors among 13 of 41 sera obtained from patients with different types of epithelial malignancies. Overall, serum positivity was most frequently directed against ErbB2 followed by EGFR, ErbB3 and ErbB4. Specificity patterns comprised tumor patients with unique serum reactivity against ErbB2 or ErbB4. Moreover, approximately half of the positive sera exhibited concomitant reactivity with multiple ErbB receptors including EGFR and ErbB2, EGFR and ErbB4, ErbB2 and ErbB3 or EGFR, ErbB2 and ErbB3. Serum reactivity was confirmed for the respective ErbB receptors expressed by human tumor cells and corroborated on receptor-specific immunoprecipitates. Positive sera contained ErbB-specific antibodies of the IgG isotype. Representative immunohistochemical analysis of tumor tissues suggested overexpression of ErbB receptors for which serum antibodies were detectable in five of six patients. These findings implicate multiple ErbB receptors including ErbB3 and ErbB4 in addition to EGFR and ErbB2 in primary human cancer. Heterogeneity of natural ErbB-specific responses in cancer patients warrants their evaluation in light of immunotherapeutic approaches targeting these receptors.
利用携带个体人类表皮生长因子受体（ErbB）编码序列的NIH3T3转染细胞作为重组抗原来源，我们通过免疫印迹分析在41例不同类型上皮恶性肿瘤患者的血清中检测到13例对所有四种ErbB受体具有特异性免疫反应性。总体而言，血清阳性反应最常见于针对ErbB2，其次是表皮生长因子受体（EGFR）、ErbB3和ErbB4。特异性模式包括对ErbB2或ErbB4具有独特血清反应性的肿瘤患者。此外，大约一半的阳性血清对多种ErbB受体表现出伴随反应性，包括EGFR和ErbB2、EGFR和ErbB4、ErbB2和ErbB3或EGFR、ErbB2和ErbB3。通过人类肿瘤细胞表达的相应ErbB受体证实了血清反应性，并在受体特异性免疫沉淀中得到了证实。阳性血清含有IgG同种型的ErbB特异性抗体。肿瘤组织的代表性免疫组织化学分析表明，在六名患者中的五名患者中可检测到血清抗体的ErbB受体过表达。这些发现表明，除了EGFR和ErbB2之外，原发性人类癌症中还涉及多种ErbB受体，包括ErbB3和ErbB4。癌症患者中天然ErbB特异性反应的异质性值得根据针对这些受体的免疫治疗方法对其进行评估。
