A recombinant single-chain antibody interleukin-2 fusion protein.
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 in E. 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 anti-tumor response while keeping systemic side effects to a minimum.
Savage
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P
Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London.
So
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Spooner
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RA
Epenetos
A A
AA
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001483:Base Sequence; D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D002469:Cell Separation; D002846:Chromatography, Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins