Sh. Chen et al., COMBINATION SUICIDE AND CYTOKINE GENE-THERAPY FOR HEPATIC METASTASES OF COLON-CARCINOMA - SUSTAINED ANTITUMOR IMMUNITY PROLONGS ANIMAL SURVIVAL, Cancer research, 56(16), 1996, pp. 3758-3762
The effectiveness of combination therapy using a suicide gene and cyto
kine genes for the treatment of metastatic colon carcinoma in the mous
e liver was investigated. Pre-established hepatic tumors treated with
a recombinant adenoviral vector containing the herpes simplex virus th
ymidine kinase gene (tk) exhibited substantial regression, although al
l treated animals suffered from subsequent relapses. Although cotreatm
ent with a mouse interleukin 2 (mIL-2)-containing adenoviral vector in
duced an effective antitumor immune response, the immunity waned with
time, and the treated animals eventually succumbed to hepatic tumor re
lapse or distant metastases. In this study, mouse granulocyte macropha
ge colony-stimulating factor (mGM-CSF) gene was tested for its ability
to further enhance and prolong the antitumoral cellular immunity. A f
raction of the animals treated with tk + mIL-2 + mGM-CSF developed lon
g-term antitumor immunity and survived for more than 4 months without
recurrence. This long-term antitumor immunity could be enhanced furthe
r by subsequent ''vaccination'' with mIL-2-expressing parental tumor c
ells. The results indicate that local expression of GM-CSF in the hepa
tic tumors and prolonged mIL-2 expression are necessary to generate pe
rsistent antitumor immunity that is essential for the prevention of tu
mor recurrence and long-term animal survival.