Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer.
Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer.
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发表时间：
1994
期刊：
影响因子：
11.2
通讯作者：
M. Disis;E. Calenoff;Graham McLaughlin;A. Murphy;Wei Chen;B. Groner;M. Jeschke;Nick Lydon;E. McGlynn;R. Livingston;R. Moe;M. Cheever
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作者：
M. Disis;E. Calenoff;Graham McLaughlin;A. Murphy;Wei Chen;B. Groner;M. Jeschke;Nick Lydon;E. McGlynn;R. Livingston;R. Moe;M. Cheever
HER-2/neu原癌基因在20-40%的浸润性乳腺癌中扩增和过度表达。HER-2/neu蛋白过度表达与侵袭性疾病有关，是几类患者预后不良的独立预测因子。该蛋白也可能与癌症的形成有关，在50%-60%的导管原位癌中可检测到过表达。有人建议，有可能开发针对参与恶性转化的蛋白质的特异性T细胞疗法。一个问题是，过度表达的正常蛋白质是否是治疗性免疫攻击的合适目标。部分HER-2/neu阳性乳腺癌患者既存在CD4+辅助性/诱导性T细胞免疫，又存在抗体介导的针对HER-2/neu蛋白的免疫。对20名绝经前乳腺癌患者进行的初步研究发现，11人中有HER-2/neu抗体。在一些正常人身上也发现了类似的抗体反应。对抗体反应最强的患者进行了详细研究。除了体液免疫反应外，该患者还有证据表明对HER-2/neu蛋白和多肽有显着的增殖性T细胞反应。在其他患者中也检测到了类似的T细胞反应。人们一直认为患者对作为自身蛋白的HER-2/neu具有免疫耐受性，而免疫可能很难产生。如果能产生免疫力，结果可能是破坏性的自身免疫。目前的数据支持HER-2/neu特异性免疫可能在不破坏正常组织的情况下用于治疗的观点，但也提出了现有免疫在免疫监测和癌症进展中的作用的问题。
The HER-2/neu protooncogene is amplified and overexpressed in 20-40% of invasive breast cancers. HER-2/neu protein overexpression is associated with aggressive disease and is an independent predictor of poor prognosis in several subsets of patients. The protein may also be related to cancer formation, with overexpression being detectable in 50-60% of ductal carcinomas in situ. It has been suggested that it might be possible to develop specific T-cell therapy directed against proteins involved in malignant transformation. One question is whether normal proteins that are overexpressed are appropriate targets for therapeutic immune attack. This report demonstrates that some patients with HER-2/neu-positive breast cancers have both existent CD4+ helper/inducer T-cell immunity and antibody-mediated immunity to HER-2/neu protein. Initial studies performed on 20 premenopausal breast cancer patients identified antibodies to HER-2/neu in 11 individuals. Similar antibody responses have been found in some normal individuals. The patient with the greatest antibody response was studied in detail. In addition to a humoral immune response this patient had evidence of a significant proliferative T-cell response to the HER-2/neu protein and peptides. Similar T-cell responses have been detected in additional patients. It has been assumed that patients would be immunologically tolerant to HER-2/neu as a self-protein and that immunity might be difficult to generate. If immunity could be generated, the result might be destructive autoimmunity. The current data support the notion that HER-2/neu-specific immunity might be used in therapy without destroying normal tissue but also raises questions as to the role of existent immunity in immune surveillance and cancer progression.