Inhibition of tumor growth by histoincompatible cells expressing interleukin-2.
Murine tumor cells engineered to express IL-2 have been shown to be rejected by the syngeneic host, which is then protected against a subsequent tumorigenic challenge. To assess whether IL-2 has to be produced by the tumor cells themselves, or whether its local delivery would be sufficient to promote such beneficial effects, the syngeneic tumor cells were co-inoculated with allogeneic or xenogeneic cells secreting IL-2, selected after gene transfection. In several murine systems, it was observed that this is an efficient approach for controlling the growth of the syngeneic tumor. However, animals which rejected the tumor were not protected against a subsequent challenge. Several lines of evidence indicate that NK cells play a major role in tumor rejection induced by the IL-2 expressing histoincompatible vector cells. Thus, while local delivery of IL-2 in the vicinity of a tumor might not be sufficient to promote a systemic long-term specific antitumor immune response, it can control the growth of the primary syngeneic tumor. These experiments demonstrate the feasibility of using genetically engineered histoincompatible cells (which are rejected by the host's immune system) as a transient delivery system in vivo.
Roth
C
C
U 277 INSERM, Institut Pasteur, Paris, France.
Mir
L M
LM
Cressent
M
M
Quintin-Colonna
F
F
Ley
V
V
Fradelizi
D
D
Kourilsky
P
P
D000818:Animals; D002460:Cell Line; D006084:Graft Rejection; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D015847:Interleukin-4 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D051381:Rats; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D015847:Interleukin-4