Long-lived and transferable tumor immunity in mice after targeted interleukin-2 therapy.
A major goal of tumor immunotherapy is the induction of tumor-specific T cell responses that are effective in eradicating disseminated tumor, as well as mounting a persistent tumor-protective immunity. We demonstrate here that a genetically engineered fusion protein consisting of human/mouse chimeric anti-ganglioside GD2 antibody and human interleukin-2 is able to induce eradication of established B78-D14 melanoma metastases in immunocompetent syngeneic C57BL/6J mice. This therapeutic effect is mediated by host immune cells, particularly CD8+ T cells and is associated with the induction of a long-lived immunity preventing tumor growth in the majority of animals when challenged up to four months later with B78-D14 cells. This effect was tumor-specific, since no cross-protection against syngeneic, ganglioside GD2+ EL-4 thymoma cells was observed. Furthermore, this tumor-specific protection can be transmitted horizontally to naive, syngeneic SCID mice by passive transfer of CD8+ T lymphocytes derived from immune animals. These results suggest that antibody-targeted delivery of cytokines provides a means to elicit effective immune responses against established tumors in the immunotherapy of neoplastic disease.
Becker
J C
JC
The Scripps Research Institute, Department of Immunology, La Jolla, California 92037, USA.
Varki
N
N
Gillies
S D
SD
Furukawa
K
K
Reisfeld
R A
RA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005732:Gangliosides / Q000276:immunology; D007109:Immunity; D007150:Immunohistochemistry; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D008545:Melanoma / Q000378:metabolism / Q000628:therapy; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D005732:Gangliosides; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins