ANTITUMOR EFFECT OF CD40 LIGAND - ELICITATION OF LOCAL AND SYSTEMIC ANTITUMOR RESPONSES BY IL-12 AND B7

The interaction between CD40 ligand (CD40L, CD154) and its receptor CD 40 has been implicated in the establishment of cell-mediated immunity as well as humoral immune responses. To examine the role of CD40L in e liciting antitumor immunity, we introduced murine CD40L gene into P815 mastocytoma (CD40L-P815), CD40L-P815 cells underwent prompt rejection when inoculated s.c. into syngenic DBA/2 mice or athymic BALB/c nu/nu mice, which was mediated by NK cells and dependent on endogenous IL-1 2, The primary rejection of CD40L-P815 cells in DBA/2 mice elicited CD 8(+) T cell-mediated protective and systemic immunity against parental tumor cells, which was induced by CD4(+) T cells and endogenous B7, T hese results indicated a potent antitumor effect of CD40L that is medi ated by potentiation of host Ag-presenting cell functions, and introdu ction of CD40L will be useful as a new strategy of immune-gene therapy against tumors.