Role of Interferons in the Thearpy of Melanoma
Role of Interferons in the Thearpy of Melanoma
复制标题
干扰素在黑色素瘤治疗中的作用
DOI：
10.1111/1523-1747.ep12875497
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发表时间：
1990
影响因子：
6.5
通讯作者：
M. Ernstoff
中科院分区：
文献类型：
--
作者：
J. Kirkwood;M. Ernstoff
一系列被称为细胞因子的有效免疫调节分子已经可用于治疗人类黑色素瘤。在细胞因子中，干扰素已被深入研究用于黑色素瘤的治疗。干扰素能够调节宿主效应细胞的功能，包括淋巴细胞和单核细胞的肿瘤杀伤功能。干扰素还可以调节循环免疫调节(T)淋巴细胞的分布和肿瘤细胞表面抗原的表达，以及主要组织相容性位点的I类和II类产物。干扰素的这些活性使其早期应用于人类黑色素瘤的治疗。回顾了干扰素α在临床上对黑色素瘤具有显著抗肿瘤作用的经验证据，并指出了干扰素α和伽马的佐剂试验的进展情况。新的间接宿主介导的抗肿瘤活性可能是由干扰素表现出来的，但尚未完全被利用。在晚期疾病或佐剂环境中，以低于毒性(常规最大耐受性)的剂量范围获得有意义的抗肿瘤活性的机会近在咫尺。美国合作小组[东部合作肿瘤组(ECOG)、癌症和白血病B组(CALGB)和西南肿瘤组(SWOG)]正在研究干扰素-伽马，以期在治疗黑色素瘤和其他肿瘤的晚期和辅助环境中实现这一目标。要确定干扰素作为生物反应调节剂的临床作用，需要对免疫生物学机制和抗肿瘤效应的临床评估做出同样的承诺。对干扰素和其他一些细胞因子，如白介素2(IL-2)的免疫学评估可能是最合适的，也是匹兹堡癌症研究所的一个主要关注点。考虑到它们的半衰期，地区性交付的毒性最低的方法。通过肿瘤内途径的区域治疗已经产生了一系列生物制剂的增强活性，包括卡介苗(BCG)、IL-2和肿瘤坏死因子(TNF)。卡介苗的甲醇提取残留物(Mer-BCG)的淋巴内治疗已经进行了试验，目前正在进行IL-2的试验，以评估通过这一途径的最佳剂量。干扰素和其他细胞因子的最佳作用可能是相互结合，以及与不同的生物形式，如单抗和疫苗，以允许在宿主中扩增和提高所需的效应细胞群的活性。增强的宿主毒性和抗肿瘤作用可能需要特别注意最佳给药顺序以提高治疗指数。
A range of potent immunoregulatory molecules termed cytokines has become available for the therapy of human melanoma. Among the cytokines, the interferons (IFN) have been examined in great depth for the therapy of melanoma. IFN are able to modulate host effector cell function, including the tumor cytolytic function of lymphocytes and monocytes. IFN also have the capacity to regulate the distribution of circulating immunoregulatory (T) lymphocytes and the expression of tumor cell surface antigens, as well as class I and II products of the major histocompatibility locus. These activities of the IFN have led to their early application for treatment of human melanoma. The empirical evidence that IFN alpha exerts clinically significant anti-tumor effects against melanoma is reviewed, and evolving status of adjuvant trials of IFN alpha and gamma is noted. New indirect host-mediated anti-tumor activities that may potentially be manifest by IFN have yet to be fully harnessed. The opportunity to obtain meaningful anti-tumor activity in advanced disease or adjuvant settings, at dose ranges below those which are toxic (conventional maximal tolerable), are at hand. The U.S. cooperative groups [Eastern Cooperative Oncology Group (ECOG), Cancer and Leukemia Group B (CALGB), and South West Oncology Group (SWOG)] are studying IFN gamma in pursuit of this goal in advanced and adjuvant settings for melanoma and other tumors. The determination of the clinical role of IFN as biologic response modifiers demands equal commitment to the clinical assessment of immunobiologic mechanisms and anti-tumor effects. The immunologic assessment of IFN and a number of other cytokines cytokines such as interleukin-2 (IL-2) may be the most appropriate and is a major focus of the Pittsburgh Cancer Institute. Regional delivery of least toxic approach, given their half-life. Regional therapy by the intralesional route has yielded enhanced activity for a range of biologics, including bacillus Calmette-Guerin (BCG), IL-2, and tumor necrosis factor (TNF). Intralymphatic therapy with methanol extraction residue of BCG (MER-BCG) has been tested, and trials are now in progress with IL-2 to assess the optimal dosage by this route. It is likely that the optimal role of IFN and other cytokines will be found in combination with one another, and with different biologic modalities such as monoclonal antibodies and vaccines, to allow expansion and heightened activity of the desired effector cell populations in the host. Enhanced host toxicities, as well as anti-tumor effects, may require that special attention be devoted to optimal sequence of administration to enhance the therapeutic index.
重组α2b-干扰素联合或不联合吲哚美辛治疗转移性恶性黑色素瘤患者的随机试验。
影响因子：
11.2
作者：
Miller,RL;Steis,RG;Clark,JW;Smith2nd,JW;Crum,E;McKnight,JE;Hawkins,MJ;Jones,MJ;Longo,DL;Urba,WJ
通讯作者：
Urba,WJ
康涅狄格州最近出生队列中皮肤黑色素瘤的风险。
影响因子：
12.7
作者：
Roush,GC;Schymura,MJ;Holford,TR
通讯作者：
Holford,TR