Antibody-targeted interleukin 2 stimulates T-cell killing of autologous tumor cells.
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.
Gillies
S D
SD
Research Department, Abbott Biotech, Inc., Needham Heights, MA 02194.
Reilly
E B
EB
Lo
K M
KM
Reisfeld
R A
RA
D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry; D003602:Cytotoxicity, Immunologic; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000737:chemistry; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C019403:ganglioside, GD2