A recombinant antibody-interleukin 2 fusion protein suppresses growth of hepatic human neuroblastoma metastases in severe combined immunodeficiency mice.
A genetically engineered fusion protein consisting of a human/mouse chimeric anti-ganglioside GD2 antibody (ch14.18) and recombinant human interleukin 2 (rhIL-2) was tested for its ability to target rhIL-2 to tumor sites and stimulate immune effector cells sufficiently to achieve effective tumor cell lysis in vivo. The ch14.18-IL-2 fusion protein proved more effective than equivalent doses of rhIL-2 in suppressing dissemination and growth of human neuroblastoma in an experimental hepatic metastases model of scid (severe combined immunodeficiency) mice reconstituted with human lymphokine-activated killer cells. The ch14.18-IL-2 fusion protein was also more proficient than equivalent doses of rhIL-2 in prolonging the life-span of these animals. This recombinant antibody-cytokine fusion protein may prove useful for future treatment of GD2-expressing human tumors in an adjuvant setting.
Sabzevari
H
H
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Gillies
S D
SD
Mueller
B M
BM
Pancook
J D
JD
Reisfeld
R A
RA
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008113:Liver Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary* / Q000628:therapy; D051379:Mice; D016513:Mice, SCID; D009447:Neuroblastoma / Q000473:pathology / Q000517:prevention & control / Q000556:secondary* / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D000906:Antibodies; D005732:Gangliosides; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C019403:ganglioside, GD2