Administration of subtumor regression dosage of TNF-alpha to mice with pre-existing parental tumors augments the vaccination effect of TNF gene-modified tumor through the induction of MHC class I molecule
Y. Lu et al., Administration of subtumor regression dosage of TNF-alpha to mice with pre-existing parental tumors augments the vaccination effect of TNF gene-modified tumor through the induction of MHC class I molecule, GENE THER, 8(7), 2001, pp. 499-507
One obstacle in treating pre-existing parental tumors by vaccination with c
ytokine gene-modified tumor cells is the impaired expression of immune-rela
ted molecules such as MHC class I. In this study, to enhance MHC class I ex
pression on pre-inoculated parental tumors, low dose TNF (300 U, 500 U, 100
0 U), that is, TNF at levels shown to cause neither tumor regression nor an
y severe adverse reaction, was systemically injected into parental tumors b
earing mice before vaccination with TNF gene-modified Meth-A cells or B-16
cells. Since the class I expression was confirmed to continue for at least
24 h following administration of TNF, TNF was administered 6 h before vacci
nation. Complete regression of relatively large parental tumors (Ma) (8.0-1
0.0 mm in diameter) was observed in five of eight mice treated with 1000 U
TNF. partial regression was observed in mice treated with 500 U, and a less
er yet significant regression was observed in mice treated with only 300 U.
Contrarily. in the mice which had received vaccination without the TNF pre
treatment no complete regression was observed. This effect was inhibited wi
th the anti-class I antibody or anti-CD8 antibody. Growth of a reestablishe
d, B16 tumor was significantly suppressed with a combination of TNF preadmi
nistration and vaccination of TNF gene-modified B16. These results indicate
that preadministration of low-dose TNF may be promising for enhancing vacc
ination effects of TNF gene-modified tumor cells.