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

Citation
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
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
GENE THERAPY
ISSN journal
0969-7128 → ACNP
Volume
8
Issue
7
Year of publication
2001
Pages
499 - 507
Database
ISI
SICI code
0969-7128(200104)8:7<499:AOSRDO>2.0.ZU;2-N
Abstract
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.