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Mechanism of Action and Pharmacokinetics of Approved Bispecific Antibodies

機(jī)譯：已獲批雙特異性抗體的作用機(jī)制和藥代動(dòng)力學(xué)

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Bispecific antibodies represent a significant advancement in therapeutic antibody engineering, offering the ability to simultaneously target two distinct antigens. This dual-targeting capability enhances therapeutic efficacy, especially in complex diseases, such as cancer and autoimmune disorders, where drug resistance and incomplete target coverage are prevalent challenges. Bispecific antibodies facilitate immune cell engagement and disrupt multiple signaling pathways, providing a more comprehensive treatment approach than traditional monoclonal antibodies. However, the intricate structure of bispecific antibodies introduces unique pharmacokinetic challenges, including issues related to their absorption, distribution, metabolism, and excretion, which can significantly affect their efficacy and safety. This review provides an in-depth analysis of the structural design, mechanisms of action, and pharmacokinetics of the currently approved bispecific antibodies. It also highlights the engineering innovations that have been implemented to overcome these challenges, such as Fc modifications and advanced dimerization techniques, which enhance the stability and half-life of bispecific antibodies. Significant progress has been made in bispecific antibody technology; however, further research is necessary to broaden their clinical applications, enhance their safety profiles, and optimize their incorporation into combination therapies. Continuous advancements in this field are expected to enable bispecific antibodies to provide more precise and effective therapeutic strategies for a range of complex diseases, ultimately improving patient outcomes and advancing precision medicine.
機(jī)譯：雙特異性抗體代表了治療性抗體工程的重大進(jìn)步，能夠同時(shí)靶向兩種不同的抗原。這種雙靶向能力增強(qiáng)了治療效果，尤其是在癌癥和自身免疫性疾病等復(fù)雜疾病中，這些疾病的耐藥性和不完全的靶點(diǎn)覆蓋是普遍的挑戰(zhàn)。雙特異性抗體可促進(jìn)免疫細(xì)胞參與并破壞多種信號(hào)通路，提供比傳統(tǒng)單克隆抗體更全面的治療方法。然而，雙特異性抗體的復(fù)雜結(jié)構(gòu)帶來(lái)了獨(dú)特的藥代動(dòng)力學(xué)挑戰(zhàn)，包括與其吸收、分布、代謝和排泄相關(guān)的問(wèn)題，這些問(wèn)題會(huì)顯著影響其療效和安全性。本文對(duì)目前批準(zhǔn)的雙特異性抗體的結(jié)構(gòu)設(shè)計(jì)、作用機(jī)制和藥代動(dòng)力學(xué)進(jìn)行了深入分析。它還強(qiáng)調(diào)了為克服這些挑戰(zhàn)而實(shí)施的工程創(chuàng)新，例如 Fc 修飾和先進(jìn)的二聚化技術(shù)，這些技術(shù)可以提高雙特異性抗體的穩(wěn)定性和半衰期。雙特異性抗體技術(shù)取得了重大進(jìn)展;然而，需要進(jìn)一步的研究來(lái)擴(kuò)大它們的臨床應(yīng)用，提高它們的安全性，并優(yōu)化它們與聯(lián)合療法的結(jié)合。該領(lǐng)域的持續(xù)進(jìn)步有望使雙特異性抗體能夠?yàn)橐幌盗袕?fù)雜疾病提供更精確和有效的治療策略，最終改善患者的預(yù)后并推進(jìn)精準(zhǔn)醫(yī)學(xué)。

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