Intraperitoneal administration of pMP6/liposome complexes inhibits the growth of co-localized colon-26 adenocarcinoma cells by inducing a tumor-specific immune response.
BACKGROUND
In our previous study, we found complexes of the non-coding pMP6 plasmid and cationic liposomes which exerted antitumor activity in the C26 model. We now sought to unravel the underlying protective effector mechanism(s).


METHODS
C26 recipients (i.p.; day 0) were injected once (day -2) or twice (days -2 and 2) with pMP6/liposome complexes. Thus treated mice were evaluated for tumor growth and the occurrence of innate and specific immune responses.


RESULTS
A single pMP6/liposome injection prolonged the survival of the animals as compared to non-treated C26 recipients (median survival 28 vs. 19 days). Two injections not only prolonged the survival time (median survival 55 days) but completely prevented tumor development in 50% of C26 recipients. I.p. administration of pMP6/liposome complexes resulted in the expression of the proinflammatory cytokines IL-6, IFN-gamma and TNF-alpha. This was followed by the appearance of activated NK cells within the peritoneal cavity and, somewhat later, by the induction of C26-specific CTLs. T cell depletion studies demonstrated the latter to be critical for the protective effect to occur.


CONCLUSIONS
Our data suggests that co-application of tumor cells and immunostimulatory pDNA/liposome complexes induces a protective and tumor-specific T cell response. Therefore these complexes may be considered promising agents in the immunological gene therapy of cancer.
Department of General Surgery, University of Vienna Medical School, Vienna, Austria.
Sanda
S
Sturlan
Achim
A
Schneeberger
Min
M
Fang
Britta G
BG
Beinhauer
Petra
P
Lührs
Raphaela
R
Kutil
Barbara
B
Wessner
Leaf
L
Huang
Ansgar O
AO
Aasen
Michael A
MA
Rogy
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000235:genetics; D004337:Drug Carriers; D005260:Female; D008081:Liposomes / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000627:therapeutic use*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016207:Cytokines; D004337:Drug Carriers; D008081:Liposomes