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与破伤风毒素C片段融合的单链Fv的DNA疫苗可诱导针对淋巴瘤和骨髓瘤的保护性免疫。

DNA vaccines with single-chain Fv fused to fragment C of tetanus toxin induce protective immunity against lymphoma and myeloma.

作者信息

King C A, Spellerberg M B, Zhu D, Rice J, Sahota S S, Thompsett A R, Hamblin T J, Radl J, Stevenson F K

机构信息

Tenovus Laboratory, Southampton University Hospitals Trust, England.

出版信息

Nat Med. 1998 Nov;4(11):1281-6. doi: 10.1038/3266.

Abstract

Vaccination with idiotypic protein protects against B-cell lymphoma, mainly through anti-idiotypic antibody. For use in patients, DNA vaccines containing single-chain Fv derived from tumor provide a convenient alternative vaccine delivery system. However, single-chain Fv sequence alone induces low anti-idiotypic response and poor protection against lymphoma. Fusion of the gene encoding fragment C of tetanus toxin to single-chain Fv substantially promotes the anti-idiotypic response and induces strong protection against B-cell lymphoma. The same fusion design also induces protective immunity against a surface Ig-negative myeloma. These findings indicate that fusion to a pathogen sequence allows a tumor antigen to engage diverse immune mechanisms that suppress growth. This fusion design has the added advantage of overcoming potential tolerance to tumor that may exist in patients.

摘要

用独特型蛋白进行疫苗接种主要通过抗独特型抗体预防B细胞淋巴瘤。对于患者使用而言,含有源自肿瘤的单链Fv的DNA疫苗提供了一种便捷的替代疫苗递送系统。然而,仅单链Fv序列诱导的抗独特型反应较低,对淋巴瘤的保护作用较差。将破伤风毒素C片段编码基因与单链Fv融合可显著促进抗独特型反应,并诱导对B细胞淋巴瘤的强大保护作用。相同的融合设计还可诱导针对表面Ig阴性骨髓瘤的保护性免疫。这些发现表明,与病原体序列融合可使肿瘤抗原参与多种抑制生长的免疫机制。这种融合设计还具有克服患者体内可能存在的对肿瘤潜在耐受性的额外优势。

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