Treatment of glioma by engineered interleukin 4-secreting cells.
The ability of interleukin-4 (IL-4) to mediate an antitumor response to human gliomas was studied in vivo in nude mice. To allow the effect of IL-4 to be exerted over a relatively short distance and at an optimal concentration, a transfected tumor cell line expressing a high level of IL-4 was used in mixed tumor transplantation assays. There was a significant inhibition of growth of the U87 human glioma line when the IL-4-secreting cell line, LT-1, was implanted s.c. with the glioma in 5 nude mice when compared to contralateral control tumors consisting of the U87 glioma and IL-4-negative control cells. In addition, there was a prolongation of survival when U87 along with IL-4-secreting cells were implanted intracerebrally in 12 nude mice compared to 12 control nude mice implanted with U87 and IL-4-negative control cells and 11 control animals receiving U87 alone. Histological analysis 4 days after i.c. inoculation revealed the presence of a dramatic eosinophil infiltrate and tumor necrosis. The absence of viable glioma cells as well as resolution of inflammation 19 days after treatment suggests the potential for complete tumor regression without ongoing inflammatory sequelae resulting from cytokine treatment.
Yu
J S
JS
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Wei
M X
MX
Chiocca
E A
EA
Martuza
R L
RL
Tepper
R I
RI
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001932:Brain Neoplasms / Q000628:therapy*; D005260:Female; D005910:Glioma / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D015847:Interleukin-4 / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010954:Plasmacytoma / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D011994:Recombinant Proteins; D015847:Interleukin-4