CEACAM1 is a Privileged Cell Surface Antigen to Design Novel ScFv Mediated-Immunotherapies of Melanoma, Lung Cancer and Other Typesof Tumors

M. Cianfriglia, V. Fiori, S. Dominici, S. Zamboni, M. Flego, M. Dupuis, A. Ascione, Mara Gellini, A. Mallano, M. Magnani
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引用次数: 5

Abstract

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell surface glycoprotein involved in intercellular binding, belonging to the immunoglobulin superfamily. It is involved in cell-cell recognition and modulates cellular processes that range from vascular angiogenesis to the regulation of insulin homeostasis and T-cell proliferation. Aberrant expression of CEACAM1 is often associated with progression and metastatic potential in melanoma, lung carcinoma and other types of tumor. Tumor-specific antigens such as CEACAM1 are ideal targets for cancer immunotherapy because they are over-expressed by the cancer cell and not on non-malignant tissues, minimizing the risk of autoimmune destruction. Many of the limitations of therapeutic use of rodent monoclonal antibodies (mAbs) can now be overcome by exploiting the use of recombinant antibody fragments and the advances in antibody engineering methods to improve tumor retention, reduce immunogenicity and modulate pharmacokinetics. In addition, a novel effective model of immunotherapeutic treatments of tumors includes antibody drug conjugates (ADCs) that combine specific mAbs and antibody fragments with cytotoxic drugs, proteins, enzymes, radionuclides and nanoparticles. This review aims to describe how these antibody engineering approaches can meet the challenges for generating new and effective antibody constructs for diagnosis and therapy of CEACAM1 expressing malignancies.
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CEACAM1是一种特殊的细胞表面抗原,可用于设计新的ScFv介导的黑色素瘤、肺癌和其他类型肿瘤的免疫疗法
癌胚抗原相关细胞粘附分子1 (CEACAM1)是一种参与细胞间结合的细胞表面糖蛋白,属于免疫球蛋白超家族。它参与细胞-细胞识别,并调节从血管生成到胰岛素稳态和t细胞增殖的细胞过程。CEACAM1的异常表达通常与黑色素瘤、肺癌和其他类型肿瘤的进展和转移潜力有关。肿瘤特异性抗原(如CEACAM1)是癌症免疫治疗的理想靶点,因为它们在癌细胞中过度表达,而不是在非恶性组织中过度表达,从而最大限度地降低了自身免疫破坏的风险。现在,利用重组抗体片段和抗体工程方法的进步,可以克服啮齿动物单克隆抗体(mAbs)治疗使用的许多局限性,以改善肿瘤保留,降低免疫原性和调节药代动力学。此外,一种新的有效的肿瘤免疫治疗模型包括抗体药物偶联物(adc),它将特异性单克隆抗体和抗体片段与细胞毒性药物、蛋白质、酶、放射性核素和纳米颗粒结合起来。这篇综述的目的是描述这些抗体工程方法如何能够满足产生新的和有效的用于诊断和治疗表达CEACAM1的恶性肿瘤的抗体结构的挑战。
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