Anti-tumor immunity elicited by a recombinant vaccinia virus expressing CD70 (CD27L).
CD70, a ligand of the T cell costimulatory receptor CD27, is expressed mainly on activated B cells and has been shown to increase cytotoxic activity and 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 vitro and in vivo. In a whole tumor cell vaccine model, the growth of CD70-negative murine colon adenocarcinoma (MC38) tumor cells infected with rV-CD70 (multiplicity of infection [MOI] of 0.1) and transplanted into syngeneic C57BL/6 mice was inhibited completely while control tumors infected with wild-type vaccinia grew rapidly and killed mice within 3-5 weeks. Tumor-free mice previously immunized with rV-CD70-infected tumors were partially protected against rechallenge with wild-type tumors, demonstrating the induction of systemic anti-tumor immunity. In addition, immunization of C57BL/6 mice with rV-CD70 admixed with vaccinia virus encoding carcinoembryonic antigen (rV-CEA) was superior to treatment with rV-CEA alone in inducing CEA-specific lymphoproliferative T cell responses and reducing growth of murine colon carcinomas transduced with CEA. These studies demonstrate for the first time the potential utility of a recombinant vaccinia virus expressing CD70 to enhance T cell responses and mediate anti-tumor immunity.
Lorenz
M G
MG
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA.
Kantor
J A
JA
Schlom
J
J
Hodge
J W
JW
D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD; D053282:CD27 Ligand; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000637:transplantation / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D053282:CD27 Ligand; D019496:Cancer Vaccines; C505772:Cd70 protein, mouse; D008565:Membrane Proteins; D011994:Recombinant Proteins