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 en coding 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. T he purpose of this study was to evaluate the capacity of a combined express ion 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 e ither CD70 or CD80, The resulting cell strains Colo679-CD70, -CD80 and -CD7 0/CD80 showed strong expression of CD70, CD80 or both, respectively. As exp ected, the T-cell response to CD70-positive malignant melanoma cells was su bstantially weaker than to the CD80-positive cells. However, the combined e xpression of CD70 and CD80 resulted in a T-cell response clearly superior t o the single expression of CD80 or CD70 alone. These results provide eviden ce that CD70 plays an additional role in T-cell activation and should be co nsidered as a molecule of interest in the design of immune gene therapy str ategies for the treatment of malignant melanoma.