VACCINATION WITH B7-1(-PEPTIDE (FC-336) EFFICIENTLY INDUCE ANTIMETASTATIC EFFECT() TUMOR AND ANTIADHESION THERAPY WITH RGD PSEUDO)

We have previously shown that expression of costimulatory ligand B7-1 on MHC class I+ tumor cells (B16-BL6 melanoma) resulted in marked redu ction of lung metastasis caused by i.v. injection into immunocompetent syngeneic mice and led to induction of immunity to the challenge by t he parental B7-1 negative tumor. Here we investigated the effectivenes s of irradiated B7-1 transfected tumor cells as a vaccine on establish ed tumor metastasis and whether or not expression of B7-1 molecule on tumor cells in combination with administration of anti-adhesion peptid e FC-336 can augment the antimetastatic efficacy. Immunization with X- irradiated B7-1 transfectants after i.v. injection of B7-1(-) parental B16-BL6 cells was effective in inhibiting lung metastasis. We also fo und that vaccination with irradiated B7-1 transfectants after excision of primary tumor on day 21 resulted in significant inhibition of spon taneous lung metastasis by intrafootpad injection of viable parental B 16-BL6 melanoma, as compared with the untreated control. However, immu nizing twice with mock transfectants did not affect inhibition of spon taneous lung metastasis of wild-type tumors. On the other hand, multip le administration of a pseudo-peptide of RGD sequence (FC-336) after t umor inoculation inhibited spontaneous lung metastasis through the int erference of tumor invasion, migration and adhesion. Combined treatmen t of B7-1 transfected tumor vaccine and anti-adhesive therapy with FC- 336 led to the augmentation of the antimetastatic effect in both exper imental and spontaneous metastasis models, as compared with either tre atment alone. B7-1- and FC-336-mediated inhibition of tumor metastasis may be mediated by different mechanisms at various steps of metastasi s, based on the regulation (promotion or inhibition) of tumor interact ion with host cells and components. (C) 1998 Rapid Science Ltd.