Anti-tumor immunity elicited by a recombinant vaccinia virus expressing CD70 (CD27L)

CD70, a ligand of the T cell costimulatory receptor CD27, is expressed main ly on activated B cells and has been shown to increase cytotoxic activity a nd proliferation of preferentially unprimed T cells, Reported herein is the construction of a recombinant vaccinia virus encoding CD70 (designated rV- CD70) and a demonstration of its biological effect on naive T cells in vitr o and ill vivo, In a whole tumor cell vaccine model, the growth of CD70-neg ative murine colon adenocarcinoma (MC38) tumor cells infected with rV-CD70 (multiplicity of infection [MOI] of 0.1) and transplanted into syngeneic C5 7BL/6 mice was inhibited completely while control tumors infected with wild -type vaccinia grew rapidly and killed mice within 3-5 weeks, Tumor-free mi ce previously immunized with rV-CD70-infected tumors were partially protect ed against rechallenge with wild-type tumors, demonstrating the induction o f systemic anti-tumor immunity, In addition, immunization of C57BL/6 mice w ith rV-CD70 admired with vaccinia virus encoding carcinoembryonic antigen ( rV-CEA) was superior to treatment with rV-CEA alone in inducing CEA-specifi c lymphoproliferative T cell responses and reducing growth of murine colon carcinomas transduced with CEA, These studies demonstrate for the first tim e the potential utility of a recombinant vaccinia virus expressing CD70 to enhance T cell responses and mediate anti-tumor immunity.