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基于聚乳酸-乙醇酸共聚物(pLGA)的微粒系统用于癌症免疫治疗

Particulate Systems Based on Poly(Lactic-co-Glycolic)Acid (pLGA) for Immunotherapy of Cancer.

作者信息

Rahimian Sima, Fransen Marieke F, Kleinovink Jan Willem, Amidi Maryam, Ossendorp Ferry, Hennink Wim E

机构信息

Universiteitsweg 99, Utrecht 3584CG, The Netherlands.

出版信息

Curr Pharm Des. 2015;21(29):4201-16. doi: 10.2174/1381612821666150901100247.

Abstract

Immunotherapy of cancer is a promising therapeutic approach which aims to eliminate malignancies by inducing or enhancing an immune response against the tumor. Immunotherapy, however, faces several challenges such as local immunosuppression in the tumor area leading to immunological tolerance. To overcome these challenges, particulate formulations such as nano- and microparticles containing immunotherapeutics have been developed to increase therapeutic efficacy and reduce toxicity of immunotherapy. Particulate formulations based on biodegradable aliphatic polyesters such as poly(lactic-co-glycolic acid) (pLGA) have been extensively used with promising results. In this review, we addressed the potential of pLGA-based particulate formulations for immunotherapy of cancer. The discussion was focused on cancer vaccines and delivery of immunomodulatory antibodies. Features and drawbacks of pLGA systems were discussed together with several examples of recently developed therapeutic cancer vaccines and antibody-loaded particulate systems. Various strategies to overcome the drawbacks and optimize the formulations were given. In conclusion, pLGA-based particulate systems are attractive carriers for development of clinically acceptable formulations in immunotherapy of cancer.

摘要

癌症免疫疗法是一种很有前景的治疗方法,旨在通过诱导或增强针对肿瘤的免疫反应来消除恶性肿瘤。然而,免疫疗法面临着诸多挑战,比如肿瘤区域的局部免疫抑制会导致免疫耐受。为了克服这些挑战,人们开发了含有免疫治疗药物的纳米颗粒和微粒等颗粒制剂,以提高免疫治疗的疗效并降低其毒性。基于可生物降解脂肪族聚酯(如聚乳酸-羟基乙酸共聚物(pLGA))的颗粒制剂已被广泛应用并取得了令人满意的结果。在这篇综述中,我们探讨了基于pLGA的颗粒制剂在癌症免疫治疗中的潜力。讨论集中在癌症疫苗和免疫调节抗体的递送方面。我们讨论了pLGA系统的特点和缺点,并列举了一些最近开发的治疗性癌症疫苗和载有抗体的颗粒系统的例子。还给出了克服缺点和优化制剂的各种策略。总之,基于pLGA的颗粒系统是开发癌症免疫治疗中临床可接受制剂的有吸引力的载体。

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