Enhanced activity of hu14.18-IL2 immunocytokine against murine NXS2 neuroblastoma when combined with interleukin 2 therapy.
Established s.c. NXS2 murine neuroblastoma tumors exhibited transient resolution after suboptimal therapy using the hu14.18-IL2 immunocytokine (IC). The hu14.18-IL2 IC is a fusion protein that has linked a molecule of interleukin 2 (IL-2) to the COOH terminus of each of the IgG heavy chains on the humanized anti-GD(2) monoclonal antibody hu14.18. To induce more potent and longer lasting in vivo antitumor effects, we tested hu14.18-IL2 IC in a regimen combining it with constant infusion IL-2 in NXS2 tumor-bearing mice. The addition of the constant infusion IL-2 augmented the antitumor response induced by treatment with the hu14.18-IL2 IC in animals with experimentally induced hepatic metastases and in animals bearing localized s.c. tumors. The combined treatment induced prolonged tumor eradication in most animals bearing s.c. tumors and involved both natural killer cells and T cells. The enhanced ability of this combined treatment to prevent tumor recurrence was not observed when a larger dose of hu14.18-IL2 IC, similar in IL-2 content to the IC plus systemic IL-2 regimen, was tested as single-agent therapy. Animals showing prolonged tumor eradication of established tumors after the combined hu14.18-IL2 plus IL-2 regimen exhibited a protective T-cell-dependent antitumor memory response against NXS2 rechallenge.
Department of Human Oncology, University of Wisconsin-Madison, Madison, Wisconsin 53792, USA.
Zane C
ZC
Neal
Jeannie C
JC
Yang
Alexander L
AL
Rakhmilevich
Ilia N
IN
Buhtoiarov
Hillary E
HE
Lum
Michael
M
Imboden
Jacquelyn A
JA
Hank
Holger N
HN
Lode
Ralph A
RA
Reisfeld
Stephen D
SD
Gillies
Paul M
PM
Sondel
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008815:Mice, Inbred Strains; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009447:Neuroblastoma / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C019403:ganglioside, GD2