Vaccination of tumor cells transfected with the B7-1 (CD80) gene induces the anti-metastatic effect and tumor immunity in mice.
The present study demonstrates that the transfection of B7-1 or its variant MB7-2 genes into MHC class I+ tumor cells (B16-BL6 or K1735-M2 melanoma) resulted in the remarkable reduction of lung metastasis caused by i.v. injection into immunocompetent syngeneic mice. However, i.v. injection of the transfectants into T cell-deficient nude mice did not affect reduction of lung tumor colonies as compared with parental wild-type tumors, suggesting that such an inhibitory effect was closely associated with T cell-mediated responses. The reduced metastasis of B7+ tumor cells consequently led to the significant prolongation of survival. Expression of B7 on tumor cells did not influence the tumorigenicity in vivo and tumor cell invasion into basement membrane Matrigel in vitro. We also found that immunization of X-irradiated B7 transfectants was effective as a tumor vaccine for preventing lung metastasis caused by i.v. injection of B7- parental B16-BL6 cells but not against other syngeneic 3LL tumors. Thus, the B7-mediated anti-metastatic effect was tumor-specific. Vaccinations of irradiated B7+ tumor cells before and after surgical excision of the s.c. inoculated primary B7- tumors on day 21 achieved effectively the prevention of spontaneous lung metastasis. Our report that vaccination of irradiated B7+ tumor cells led to a therapeutic effect in an established tumor metastasis model clearly expands and confirms previous related observations.
Fujii
H
H
Research Institute for Wakan-Yaku, Toyama Medical and Pharmaceutical University, Japan.
Inobe
M
M
Kimura
F
F
Murata
J
J
Murakami
M
M
Onishi
Y
Y
Azuma
I
I
Uede
T
T
Saiki
I
I
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology*; D005260:Female; D008546:Melanoma, Experimental / Q000276:immunology / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014611:Vaccination
D018122:B7-1 Antigen