Innate immunity mediated by the cytokine IL-1 homologue 4 (IL-1H4/IL-1F7) induces IL-12-dependent adaptive and profound antitumor immunity.
Recently, several novel members of the IL-1 family have been identified. The possible therapeutic utility and the underlying biologic role of these new members remain unclear. In the present study we analyzed the anti-tumor activity of human IL-1 homologue 4(IL-1H4; renamed IL-F7) by adenovirus-mediated gene transfer (AdIL-1H4) directly into murine tumors. In vitro expression analysis showed that IL-1H4 was a secretory protein. Treatment of an established MCA205 mouse fibrosarcoma by single intratumoral injection of AdIL-1H4 resulted in significant growth suppression. Furthermore, complete inhibition of tumor growth was observed following multiple injections of AdIL-1H4. The anti-tumor activity of IL-1H4 was abrogated in nude and SCID mice and in IL-12-, IFN-gamma-, or Fas ligand-deficient mice. In contrast, IL-1H4 was able to confer substantial anti-tumor effects in NKT-deficient mice. These results suggest that IL-1H4 could play an important role in the link between innate and adaptive immunity and may be useful for tumor immunotherapy.
Gao
Wentao
W
Department of Molecular Genetics, University of Pittsburgh, PA 15219, USA.
Kumar
Sanjay
S
Lotze
Michael T
MT
Hanning
Charles
C
Robbins
Paul D
PD
Gambotto
Andrea
A
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D005354:Fibrosarcoma / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000627:therapeutic use; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D007110:Immunity, Active / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D018664:Interleukin-12 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011995:Recombination, Genetic; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D007375:Interleukin-1; C471352:interleukin-1 homolog 4, human; D018664:Interleukin-12