Targeted drug delivery for cancer therapy: the other side of antibodies.
Targeted drug delivery for cancer therapy: the other side of antibodies.
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DOI：
10.1186/1756-8722-5-70
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发表时间：
2012-11-09
影响因子：
28.5
通讯作者：
Gellerman G
中科院分区：
文献类型：
--
作者：
Firer MA;Gellerman G
基于治疗性单克隆抗体（TMA）的癌症疗法在过去二十年中在其分子复杂性和临床功效方面都有显著进步。最初的开发工作主要集中在人源化抗体蛋白以克服免疫原性问题和扩大靶抗原库。与裸TMA平行，已经开发了抗体-药物缀合物（ADC）用于靶向递送强效抗癌药物，目的是绕过常规化疗常见的发病率。本文首先介绍了FDA批准用于临床使用的TMA和ADC以及正在开发的TMA和ADC的综述，重点关注血液恶性肿瘤。尽管在这些领域取得了进展，但TMA和ADC仍然存在局限性，我们强调了更重要的局限性，包括癌细胞特异性，缀合化学，肿瘤渗透，产品异质性和制造问题。鉴于公认的重要性，有针对性的药物输送策略的癌症治疗，我们讨论了替代药物载体的优势，这些应该应用，重点是肽-药物偶联物（PDCs），特别是那些发现通过组合肽库。通过定义裸TMA、ADC和PDC的优点和缺点，应该可以开发出一种更合理的方法来在不同情况下应用靶向药物递送策略，并最终为癌症患者提供更广泛的更有效的治疗方法。
Therapeutic monoclonal antibody (TMA) based therapies for cancer have advanced significantly over the past two decades both in their molecular sophistication and clinical efficacy. Initial development efforts focused mainly on humanizing the antibody protein to overcome problems of immunogenicity and on expanding of the target antigen repertoire. In parallel to naked TMAs, antibody-drug conjugates (ADCs) have been developed for targeted delivery of potent anti-cancer drugs with the aim of bypassing the morbidity common to conventional chemotherapy. This paper first presents a review of TMAs and ADCs approved for clinical use by the FDA and those in development, focusing on hematological malignancies. Despite advances in these areas, both TMAs and ADCs still carry limitations and we highlight the more important ones including cancer cell specificity, conjugation chemistry, tumor penetration, product heterogeneity and manufacturing issues. In view of the recognized importance of targeted drug delivery strategies for cancer therapy, we discuss the advantages of alternative drug carriers and where these should be applied, focusing on peptide-drug conjugates (PDCs), particularly those discovered through combinatorial peptide libraries. By defining the advantages and disadvantages of naked TMAs, ADCs and PDCs it should be possible to develop a more rational approach to the application of targeted drug delivery strategies in different situations and ultimately, to a broader basket of more effective therapies for cancer patients.
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影响因子：
3
作者：
Daniels, Tracy R.;Bernabeu, Ezequiel;Rodriguez, Jose A.;Patel, Shabnum;Kozman, Maggie;Chiappetta, Diego A.;Holler, Eggehard;Ljubimova, Julia Y.;Helguera, Gustavo;Penichet, Manuel L.
通讯作者：
Penichet, Manuel L.
影响因子：
20.3
作者：
Beers, Stephen A.;French, Ruth R.;Cragg, Mark S.
通讯作者：
Cragg, Mark S.
影响因子：
11.5
作者：
Flessner, MF;Choi, J;Henderson, K
通讯作者：
Henderson, K
影响因子：
4.8
作者：
Cohen, Shmuel;Cahan, Rivka;Firer, Michael A.
通讯作者：
Firer, Michael A.
影响因子：
45.3
作者：
Burris, Howard A., III;Rugo, Hope S.;O'Shaughnessy, Joyce A.
通讯作者：
O'Shaughnessy, Joyce A.