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 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.
Savage
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P
Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
So
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Spooner
R A
RA
Epenetos
A A
AA
D000595:Amino Acid Sequence; D000906:Antibodies / Q000494:pharmacology; D001483:Base Sequence; D002846:Chromatography, Affinity; D005240:Feasibility Studies; D005434:Flow Cytometry; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000494:pharmacology; D007147:Immunoglobulin Light Chains / Q000494:pharmacology; D000922:Immunotoxins / Q000494:pharmacology; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D009113:Muramidase / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects
D000906:Antibodies; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D000922:Immunotoxins; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D009113:Muramidase