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解锁细胞内肿瘤靶点:抗体类 T 细胞受体模拟物(TCRm)疗法在 T 细胞衔接器(TCE)和抗体偶联药物(ADC)中的独特作用

英文原题:Unlocking Intracellular Oncology Targets: The Unique Role of Antibody-Based T-Cell Receptor Mimic (TCRm) Therapeutics in T-Cell Engagers (TCEs) and Antibody-Drug Conjugates (ADCs).

查看英文原题

Unlocking Intracellular Oncology Targets: The Unique Role of Antibody-Based T-Cell Receptor Mimic (TCRm) Therapeutics in T-Cell Engagers (TCEs) and Antibody-Drug Conjugates (ADCs).

PubMed 2024/11/08(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

在肿瘤学中,有效靶向细胞内肿瘤相关蛋白一直是重大挑战,因为这类蛋白传统上被认为无法通过常规抗体疗法和CAR-T 细胞疗法触及。然而,抗体工程的近期进展改变了这一局面,带来了有前景的新型抗癌策略。本综述聚焦T细胞受体模拟(TCRm)抗体在T细胞衔接器(TCE)和抗体药物偶联物(ADC)治疗框架中的创新应用。TCRm抗体识别的是肽-MHC复合物,而非细胞表面蛋白,因此结合了T细胞触及细胞内靶点的能力与抗体的独特优势。纳入T细胞衔接治疗后,TCRm可将T细胞重新定向至癌细胞,促进直接细胞毒作用。在ADC中,TCRm抗体能够将细胞毒性药物精准递送至癌细胞,同时保护健康组织。这些抗体疗法策略共同代表肿瘤治疗的一项重大进展,为此前被认为无法治疗的癌症开辟新途径,并可能应用于自身免疫性疾病。本综述讨论这些前沿疗法的作用机制、临床进展和未来前景,并强调其改变癌症治疗格局的潜力。

展开英文摘要原文

Effectively targeting intracellular tumor-associated proteins presents a formidable challenge in oncology, as they are traditionally considered inaccessible to conventional antibody-based therapies and CAR-T cell therapies.

However, recent advancements in antibody engineering have revolutionized this field, offering promising new strategies to combat cancer. This review focuses on the innovative use of T-cell receptor mimic (TCRm) antibodies within the therapeutic frameworks of T-cell engagers (TCE) and antibody-drug conjugates (ADCs).

TCRm antibodies, designed to recognize peptide-MHC complexes rather than cell surface proteins, integrate the capacity of T-cells to reach intracellular targets with the unique strengths of antibodies. When incorporated into T-cell engaging therapeutics, TCRms redirect T cells to cancer cells, facilitating direct cytotoxicity. In ADCs, TCRm antibodies deliver cytotoxic agents with highly specific targeting to cancer cells, sparing healthy tissues.

Together, these antibody-based strategies represent a significant leap forward in oncology, opening new avenues for the treatment of cancers previously deemed untreatable, with other potential applications in autoimmune diseases. This review discusses the mechanisms, clinical advancements, and future prospects of these cutting-edge therapies, highlighting their potential to transform the landscape of cancer treatment.

论文信息

作者
Molldrem J、Zha D
第一作者单位
Department of Hematopoietic Biology and Malignancy, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.United States
通讯作者单位
Alloy Therapeutics, 275 2nd Avenue, Waltham, MA 02451, USA.United States
文献类型
综述
期刊
Cancers2024 Nov 8
原文标识
PubMed 39594730 · DOI 10.3390/cancers16223776