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针对非恶性疾病中表达的疾病相关抗原 (DAA) 的抗体揭示了潜在的新的肿瘤相关抗原 (TAA),可用于免疫治疗或免疫预防。

Antibodies specific for disease-associated antigens (DAA) expressed in non-malignant diseases reveal potential new tumor-associated antigens (TAA) for immunotherapy or immunoprevention.

机构信息

Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.

Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.

出版信息

Semin Immunol. 2020 Feb;47:101394. doi: 10.1016/j.smim.2020.101394. Epub 2020 Apr 6.

Abstract

Immune responses to a large number of mutated and non-mutated tumor antigens have been studied in an attempt to unravel the highly complex immune response to cancer. Better understanding of both the effectors and the targets of successful immunosurveillance can inform various immunotherapeutic approaches, which can strengthen or replace natural immunosurveillance that a tumor has managed to escape. In this review we highlight targets of antibodies generated in the context of diseases other than cancer, such as asthma, allergies, autoimmune disorders, inflammation and infections, where the antibody presence correlates either with an increased or a reduced lifetime risk of cancer. We focus on their target antigens, self-molecules abnormally expressed on diseased cells or cross-reactive with exogenous antigens and found on cancer cells as tumor associated antigens (TAA). We refer to them as disease-associated antigens (DAA). We review 4 distinct categories of antibodies according to their target DAA, their origin and their reported impact on cancer risk: natural antibodies, autoantibodies, long-term memory antibodies and allergy-associated antibodies. Increased understanding and focus on their specific targets could enable a more rational choice of antigens for both therapeutic and preventative cancer vaccines and other more effective and less toxic cancer immunotherapies.

摘要

人们研究了针对大量突变和非突变肿瘤抗原的免疫反应,试图揭示对癌症的高度复杂的免疫反应。更好地了解成功免疫监视的效应物和靶标,可以为各种免疫治疗方法提供信息,这些方法可以加强或替代肿瘤已经逃脱的自然免疫监视。在这篇综述中,我们强调了在癌症以外的疾病(如哮喘、过敏、自身免疫性疾病、炎症和感染)背景下产生的抗体的靶标,这些抗体的存在与癌症的终生风险增加或降低相关。我们专注于它们的靶抗原,即异常表达在患病细胞上的自身分子或与外源性抗原交叉反应并在癌细胞上作为肿瘤相关抗原(TAA)存在的抗原。我们将它们称为疾病相关抗原(DAA)。我们根据目标 DAA、来源和对癌症风险的报道影响,综述了 4 种不同类别的抗体:天然抗体、自身抗体、长期记忆抗体和过敏相关抗体。增加对它们特定靶标的理解和关注,可以为治疗性和预防性癌症疫苗以及其他更有效和毒性更小的癌症免疫疗法更合理地选择抗原。

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