Antibody-Targeted Interleukin 2 Stimulates T-Cell Killing of Autologous Tumor Cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 89; no. 4; pp. 1428 - 1432
• Main Authors: Gilles, Stephen D., Reilly, Edward B., Lo, Kin-Ming, Reisfeld, Ralph A.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.02.1992; National Acad Sciences; National Academy of Sciences
• Subjects: Antibodies; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - chemistry; Antibody dependent cell cytotoxicity; Antigens; Biological and medical sciences; Cancer; Cellular immunity; Cytotoxic reactions (adcc reaction, cell-mediated lympholysis, complement-dependent cytotoxicity and others); Cytotoxicity, Immunologic; Drugs; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gangliosides - immunology; Humans; Immunity (Disease); Immunobiology; Immunological reactions in vitro; In Vitro Techniques; Interleukin-2 - administration & dosage; Interleukin-2 - chemistry; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating - immunology; Medical research; Melanoma; Melanoma - immunology; Natural killer cells; Proteins; Recombinant Fusion Proteins - pharmacology; T lymphocytes; T-Lymphocytes - immunology; Tumor cell line; Tumors; Human; Antibody; Cytokine; Melanoma; Cytotoxicity; Autologous system; In vitro; Ganglioside; Interleukin 2; Immunotherapy; Antibody-dependent cell cytotoxicity; T-Lymphocyte; Tumor; Target cell; Chimera
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.4.1428

A genetically engineered fusion protein consisting of a chimeric anti-ganglioside GD2 antibody (ch14.18) and interleukin 2 (IL2) was tested for its ability to enhance the killing of autologous GD2-expressing melanoma target cells by a tumor-infiltrating lymphocyte line (660 TIL). The fusion of IL2 to the carboxyl terminus of the immunoglobulin heavy chain did not reduce IL2 activity as measured in a standard proliferation assay using either mouse or human T-cell lines. Antigen-binding activity was greater than that of the native chimeric antibody. The ability of resting 660 TIL cells to kill their autologous GD2-positive target cells was enhanced if the target cells were first coated with the fusion protein. This stimulation of killing was greater than that of uncoated cells in the presence of equivalent or higher concentrations of free IL2. Such antibody-cytokine fusion proteins may prove useful in targeting the biological effect of IL2 and other cytokines to tumor cells and in this way stimulate their immune destruction.