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靶向碳水化合物抗原的癌症疫苗。

Cancer vaccines targeting carbohydrate antigens.

作者信息

Livingston Philip O, Ragupathi Govind

机构信息

Laboratory of Tumor Vaccinology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

出版信息

Hum Vaccin. 2006 May-Jun;2(3):137-43. doi: 10.4161/hv.2941. Epub 2006 May 16.

Abstract

Cancer carbohydrate antigens have been surprisingly potent targets for immune recognition and attack by antibodies, both because of their abundance at the cell surface and their immunogenicity. Antibodies are ideally suited for eradicating pathogens from the bloodstream and from early tissue invasion. Passively administered and vaccine induced antibodies have accomplished this, eliminating circulating tumor cells and systemic or intraperitoneal micrometastases in a variety of preclinical models. A series of carbohydrate cancer cell-surface differentiation antigens have now been identified and synthesized. Antibodies against each can be induced in the majority of vaccinated patients using KLH conjugate vaccines with a potent saponin immunological adjuvant. Polyvalent vaccines will probably be required due to tumor cell heterogeneity, heterogeneity of the human immune response and the correlation between overall antibody titer against tumor cells and antibody effector mechanisms. Trials testing the clinical impact of these polyvalent vaccines in the adjuvant setting are planned for the near future.

摘要

癌症碳水化合物抗原一直是抗体进行免疫识别和攻击的惊人有效靶点,这既是因为它们在细胞表面的丰度,也是因为它们的免疫原性。抗体非常适合从血液和早期组织侵袭中清除病原体。被动给药和疫苗诱导的抗体已经做到了这一点,在各种临床前模型中消除了循环肿瘤细胞以及全身或腹腔内的微转移。现在已经鉴定并合成了一系列碳水化合物癌细胞表面分化抗原。使用具有强效皂苷免疫佐剂的KLH缀合疫苗,大多数接种疫苗的患者都能诱导出针对每种抗原的抗体。由于肿瘤细胞的异质性、人类免疫反应的异质性以及针对肿瘤细胞的总体抗体滴度与抗体效应机制之间的相关性,可能需要多价疫苗。计划在不久的将来进行试验,测试这些多价疫苗在辅助治疗中的临床影响。

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