Granulocyte-macrophage colony-stimulating factor: an effective adjuvant for protein and peptide-based vaccines.
Granulocyte-macrophage colony-stimulating factor: an effective adjuvant for protein and peptide-based vaccines.
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DOI：
10.1182/blood.v88.1.202.202
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发表时间：
1996
期刊：
影响因子：
20.3
通讯作者：
M. Disis;H. Bernhard;F. Shiota;Susan;Hand;J. Gralow;S. Huseby;S. Gillis;M. Cheever
中科院分区：
文献类型：
--
作者：
M. Disis;H. Bernhard;F. Shiota;Susan;Hand;J. Gralow;S. Huseby;S. Gillis;M. Cheever
目前的研究评价粒细胞巨噬细胞集落刺激因子(GM-CSF)作为疫苗佐剂。开发针对人类恶性肿瘤的疫苗疗法的一个重要问题是确定能够激发T细胞对来自“自身”肿瘤抗原的蛋白质和多肽的反应的佐剂。在体外，GM-CSF可以刺激树突状细胞和巨噬细胞等抗原呈递细胞的生长。初步实验检测了GM-CSF注射到大鼠皮肤中是否会影响注射部位引流的淋巴结中抗原提呈细胞的数量或性质，该细胞被测量为表达II类主要组织相容性复合体的细胞。皮内接种GM-CSF，每24小时接种一次，共接种5次，II+荧光细胞数增加，在第4次接种时达到高峰。皮下接种(SQ)导致II+类荧光细胞增加，在第二次接种后达到峰值，然后随着时间的推移而减少。利用这种“调节”接种部位的方案，给GM-CSF注射5次，并在免疫周期的开始或结束时给予外来抗原破伤风类毒素(TT)。ID免疫在诱导TT特异性免疫方面比SQ更有效。与完全弗氏佐剂(CFA)和明矾单次注射相比，GM-CSFid在诱导TT特异性抗体和细胞免疫方面具有更好的效果。我们已经证明，用来自正常大鼠neu序列的多肽和CFA免疫大鼠，可以产生对大鼠neu(c-erbB-2)蛋白的免疫，这是一种致癌的自身蛋白。目前的研究表明，接种GM-CSF的大鼠Neu多肽可以引起强烈的迟发型超敏反应(DTH)，而单独接种多肽则不具有免疫原性。GM-CSF在Neu多肽疫苗免疫后产生大鼠Neu特异性DTH反应方面与CFA一样有效。可溶性GM-CSF是一种有效的佐剂，可用于产生对外来蛋白和来自自身肿瘤抗原的多肽的免疫反应。
The current studies evaluate granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant. An important issue for developing vaccine therapy for human malignancy is identifying adjuvants that can elicit T-cell responses to proteins and peptides derived from "self" tumor antigens. GM-CSF, in vitro, stimulates the growth of antigen-presenting cells such as dendritic cells and macrophages. Initial experiments examined whether GM-CSF injected into the skin of rats could affect the number or character of antigen presenting cells, measured as class II major histocompatability complex expressing cells, in lymph nodes draining the injection site. Intradermal (id) inoculation of GM-CSF every 24 hours for a total of five inoculations resulted in an increase of class II+ fluorescing cells that peaked at the fourth inoculation. Subcutaneous (sq) inoculation resulted in an increase of class II+ fluorescing cells that peaked following the second inoculation, then decreased over time. Using this schema for "conditioning" the inoculation site, GM-CSF was administered id or sq for five injections and a foreign antigen, tetanus toxoid (tt), was given at the beginning or the end of the immunization cycle. Id immunization was more effective than sq at eliciting tt specific immunity. In addition, GM-CSF id, administered as a single dose with antigen, compared favorably with complete Freund's adjuvant (CFA) and alum in eliciting tt specific antibody and cellular immunity. We have shown that immunity to rat neu (c-erbB-2) protein, an oncogenic self protein, can be generated in rats by immunization with peptides derived from the normal rat neu sequence plus CFA. The current study demonstrates that rat neu peptides inoculated with GM-CSF could elicit a strong delayed type hypersensitivity reaction (DTH) response, whereas peptides alone were non-immunogenic. GM-CSF was as effective as CFA in generating rat neu specific DTH responses after immunization with a neu peptide based vaccine. Soluble GM-CSF is a potent adjuvant for the generation of immune responses to foreign proteins as well as peptides derived from a self tumor antigen.