In vivo antitumor effect of CD40L-transduced tumor cells as a vaccine for B-cell lymphoma.
CD40-CD40 ligand (CD40L) interactions play a critical role in the activationof cellular immunity. CD40L enhances the antigen presentation function of CD40-expressing B cells. We have used a murine B-cell lymphoma model (A20) to study the in vivo antitumor effect of the administration of tumor cells transduced with a recombinant adenovirus encoding CD40L (AdvCD40L). After infection with AdvCD40L, A20 tumor cells up-regulate several T-cell costimulatory molecules (CD80, CD86, ICAM-1, and LFA-3) and Fas expression. Animals vaccinated with irradiated tumor cells transduced with AdvCD40L are protected against a lethal dose of parental A20 tumor cells. Animals with pre-existing tumors treated with AdvCD40L-transduced tumor cells display inhibition of the tumor growth, and this treatment confers a survival advantage. In vivo depletion studies demonstrate that both CD4(+) and CD8(+) T cells mediate the antitumor immunity provided by AdvCD40L-transduced tumor cells. These results show that genetic modification of tumor B cells with CD40L can be a useful strategy to promote systemic immunity against B-cell malignancies and provide an in vivo system to allow for additional evaluation and refinement of this approach.
Briones
Javier
J
Division of Oncology, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA 94305-5151, USA.
Timmerman
John
J
Levy
Ronald
R
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D005260:Female; D016233:Immunotherapy, Active; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D023201:CD40 Ligand