Efficacy of TNF-alpha gene-transduced tumor cells in treatment of established in vivo tumor.
The therapeutic effect of TNF gene-transduced mouse fibrosarcoma cells (Meth-A: C5) on pre-inoculated parental cells (Meth-A: M0) was studied. Subcutaneous (s.c.) transplantation of M0 cells into one flank of syngeneic BALB/c mice was followed by s.c. injection of irradiated MO or C5 into the opposite flank 1 week later. The initial M0 tumor (T-MO) completely regressed in C5-vaccinated mice, whereas in M0-vaccinated mice continuous growth of T-M0 was observed. When a similar experiment was carried out in SCID mice, no regression of T-MO was observed, suggesting that the tumor regression in BALB/c mice was not due to direct anti-tumor activity of TNF secreted from C5, but to systemic immunity. Regression of the rechallenged M0 tumor was observed in mice which had shown T-MO regression by C5 vaccination, but rechallenged Colon 26 cells (syngeneic to BALB/c mice) continued to grow, indicating a specific immunity to Meth-A cells). The systemic immunity evoked in C5-vaccinated mice was directly demonstrated by enhanced killer activities of LAK and CTL with a proliferation of T-cell population in their splenocytes. Abrogation of the therapeutic effect of C5 vaccination with anti-Thy 1 and anti-Lyt 2 also demonstrates the involvement of cellular immunity in tumor regression.
Koshita
Y
Y
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo City, Japan.
Lu
Y
Y
Fujii
S
S
Neda
H
H
Matsuyama
T
T
Satoh
Y
Y
Itoh
Y
Y
Takahashi
M
M
Kato
J
J
Sakamaki
S
S
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy; D007111:Immunity, Cellular; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000235:genetics
D014409:Tumor Necrosis Factor-alpha