免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Options of Therapeutics and Novel Delivery Systems of Drugs for the Treatment of Melanoma.
Options of Therapeutics and Novel Delivery Systems of Drugs for the Treatment of Melanoma.
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黑色素瘤是最严重的癌症性疾病之一。其细胞利用多种信号通路,如 ERK、HGF/c-MET、WNT 和 COX-2,导致细胞增殖、存活和转移。黑色素瘤的治疗,包括手术、化疗、免疫治疗、放疗和靶向治疗,基于该疾病的 4 个主要分期或 11 个亚分期。已有十四种药物,包括达卡巴嗪、干扰素 α-2b、白细胞介素-12、ipilimumab、聚乙二醇干扰素 α-2b、vemurafenib、trametinib、talimogene laherparepvec、cobimetinib、pembrolizumab、dabrafenib、binimetinib、encorafenib 和 nivolumab,获 FDA 批准用于治疗黑色素瘤。它们均为传统剂型,如注射液、混悬液、口服片剂或胶囊。该治疗的主要缺点在于药物副作用以及患者对其依从性不佳。这些是疾病高剂量和长期治疗的结果。目前,超过 350 项 NCI 注册的临床试验正在进行,以使用新型治疗方法治疗晚期和/或转移性黑色素瘤,如免疫细胞治疗、癌症疫苗和新的治疗靶点。
此外,利用已批准药物的生物材料开发的新型递送系统已被研发,试图提高药物递送、靶向性、稳定性、生物利用度,从而可能降低毒性并提高治疗效果。纳米颗粒和脂质体正作为先进递送系统崭露头角,可改善药物稳定性和全身循环时间。在本综述中,全面讨论了黑色素瘤治疗选择及新型药物递送系统开发的最新发现。
Melanoma is one of the most severe cancerous diseases. The cells employ multiple signaling pathways, such as ERK, HGF/c-MET, WNT, and COX-2 to cause the cell proliferation, survival, and metastasis. Treatment of melanoma, including surgery, chemotherapy, immunotherapy, radiation, and targeted therapy, is based on 4 major or 11 substages of the disease. Fourteen drugs, including dacarbazine, interferon α-2b, interleukin-12, ipilimumab, peginterferon α-2b, vemurafenib, trametinib, talimogene laherparepvec, cobimetinib, pembrolizumab, dabrafenib, binimetinib, encorafenib, and nivolumab, have been approved by the FDA for the treatment of melanoma.
All of them are in conventional dosage forms of injection solutions, suspensions, oral tablets, or capsules. Major drawbacks of the treatment are side effects of the drugs and patients' incompliance to them. These are consequences of high doses and long-term treatments for the diseases. Currently more than 350 NCI-registered clinical trials are being carried out to treat advanced and/or metastatic melanoma using novel treatment methods, such as immune cell therapy, cancer vaccines, and new therapeutic targets.
In addition, novel delivery systems using biomaterials of the approved drugs have been developed attempting to increase the drug delivery, targeting, stability, bioavailability, thus potentially reducing the toxicity and increasing the treatment effectiveness.
Nanoparticles and liposomes have been emerging as advanced delivery systems which can improve drug stability and systemic circulation time. In this review, the most recent findings in the options for treatment and development of novel drug delivery systems for the treatment of melanoma are comprehensively discussed.
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