Abstract
Recombinant interleukin-2 (rIL-2) therapy has been shown to be of value in the treatment of some cases of melanoma and renal cell carcinoma. However, its use can be limited by severe systemic toxicity. Targeting rIL-2 to the tumor should improve the antitumor 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 consists of the variable domains of the antilysozyme antibody D1.3 fused to human IL-2 and is expressed inE. coli. It retains antigen-binding specificity and has the full biological activity of rIL-2.
This approach can be taken to generate SCA-IL-2 proteins that bind to appropriate cellular antigens. In vivo administration of tumor-binding SCA-IL-2 should result in a localized high concentration of rIL-2 in the tumor tissues, maximizing the antitumor response while keeping systemic side effects to a minimum.
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Abbreviations
- rIL-2:
-
recombinant interleukin-2
- SCA:
-
single-chain antibody
- SCA-IL-2:
-
single-chain antibody interleukin-2 fusion protein
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Savage, P., So, A., Spooner, R.A. et al. A recombinant single-chain antibody interleukin-2 fusion protein. Cell Biophysics 22, 61–77 (1993). https://doi.org/10.1007/BF03033867
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DOI: https://doi.org/10.1007/BF03033867