A RECOMBINANT SINGLE CHAIN ANTIBODY INTERLEUKIN-2 FUSION PROTEIN

被引:37
作者
SAVAGE, P [1 ]
SO, A [1 ]
SPOONER, RA [1 ]
EPENETOS, AA [1 ]
机构
[1] HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT RHEUMATOL,LONDON W12 OH,ENGLAND
关键词
D O I
10.1038/bjc.1993.57
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Recombinant interleukin-2 (rIL-2) therapy has been shown to be of value in the treatment of some cases of melanoma and renal cell carinoma. However its use can be limited by severe systemic toxicity. Targeting rIL-2 to the tumour should improve the anti-tumour immune response and decrease the systemic toxicity. With this aim we have employed recombinant DNA techniques to construct a single chain antibody interleukin-2 fusion protein (SCA-IL-2). The protein used in this model system comprises the variable domains of the anti-lysozyme antibody D1.3 fused to human IL-2. It has been expressed by secretion from Escherichia coli and the purified product possesses antigen binding specificity and retains the immunostimulatory activities of rIL-2. This approach can be taken to generate SCA-IL-2 proteins that bind to appropriate cellular antigens. In vivo administration of a tumour binding SCA-IL-2 should result in a localised high concentration of IL-2 in tumour tissues, maximising the anti-tumour immune response, whilst keeping systemic side effects to a minimum.
引用
收藏
页码:304 / 310
页数:7
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