ENHANCEMENT OF ANTITUMOR IMMUNITY BY EXPRESSION OF CD70 (CD27 LIGAND)OR CD154 (CD40 LIGAND) COSTIMULATORY MOLECULES IN TUMOR-CELLS

CD70 (CD27 ligand (CD27L)), CD153 (CD30L), and CD154 (CD40L) are membe rs of the tumor necrosis factor family of costimulatory molecules and expressed on the surface of T cells that are important for both T-and B-cell help. We examined the capacity for expression of these tumor ne crosis factor family members on tumor cells to induce an antitumor res ponse either in the presence or absence of interleukin 12. Retroviral vectors were constructed that expressed high levels of membrane bound CD70, CD153, or CD154 following infection and selection of the murine tumor lines MCA 207 or TS/A. The genetically modified tumor cells expr essing these molecules were able to stimulate splenic cell proliferati on, demonstrating that the expressed costimulatory molecules were biol ogically active. When tested for tumor establishment, the expression o f either CD70 or CD154 was able to slow tumor growth. Similarly, CD70 or CD154 were able to induce antitumor immunity at a higher frequency when tested in vaccination and therapy models. CD70 was able to induce antitumor immunity at a level similar to CD80 when tested either in t he presence or absence of interleukin 12. Moreover, coexpression of CD 70 and CD80 was able to synergize the induction of a higher frequency of antitumor immunity in a vaccination model. Taken together, our resu lts suggest that CD154 and in particular CD70 are able to contribute t o the induction of the immune response to tumor in murine models and t hus may be of use for human clinical trials.