Recombinant adeno-associated virus (rAAV) vector-mediated cotransduction of CD70 and CD80 into human malignant melanoma cells results in an additive T-cell response.
Genetic modification of malignant melanoma cells by transduction of cDNA encoding costimulatory molecules, cytokines or tumor-associated antigens has been shown to induce antitumor immunity. An important step in this scenario is the activation of T cells. CD80 is a pivotal costimulatory molecule for T-cell activation. Another molecule with costimulatory activity is CD70. The purpose of this study was to evaluate the capacity of a combined expression of CD70 and CD80 on melanoma cells to amplify an antitumor response in vitro. Therefore, the CD70- and CD80-negative human malignant melanoma cell line Colo679 was transduced with adeno-associated virus vectors carrying either CD70 or CD80. The resulting cell strains Colo679-CD70, -CD80 and -CD70/CD80 showed strong expression of CD70, CD80 or both, respectively. As expected, the T-cell response to CD70-positive malignant melanoma cells was substantially weaker than to the CD80-positive cells. However, the combined expression of CD70 and CD80 resulted in a T-cell response clearly superior to the single expression of CD80 or CD70 alone. These results provide evidence that CD70 plays an additional role in T-cell activation and should be considered as a molecule of interest in the design of immune gene therapy strategies for the treatment of malignant melanoma.
Braun-Falco
M
M
Department of Dermatology, Technical University, Munich, Germany. mbf@lrz.tum.de
Hallek
M
M
D015703:Antigens, CD; D018122:B7-1 Antigen / Q000235:genetics*; D053282:CD27 Ligand; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008565:Membrane Proteins / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018122:B7-1 Antigen; D053282:CD27 Ligand; C505771:CD70 protein, human; D008565:Membrane Proteins