With this sub-project (described in the main proposal as Project 8), we intend to carry out essential tests that demonstrate that melanoma cells derived from patients respond to treatment with adenoviral vector bearing p14Arf and IFN-beta (interferon-beta). Here, we will explore the induction of cell death, the mechanism of cell death, the potential for activation of the immune system and inhibition of tumor progression in vivo. Since the immune response can not be evaluated in vivo, we will use ex vivo models for this purpose, where tumor cells will be treated with the vector, exposed to human dendritic cells (DC) and evaluated with respect to the presence of activation markers. Then, human T cells will be activated through their co-culture with the DCs. The activation state of T cells will be assessed by immunophenotyping and functional assays. In parallel, the primary human melanoma cells will be implanted s.c. of immunodeficient mice and, after tumor formation, treated with gene therapy in situ using adenovirus encoding p14Arf and IFN-Beta. We hope to reveal the reduction of tumor progression due to the induction of cell death, but this model will not reveal aspects of the immune response.
News published in Agência FAPESP Newsletter about the scholarship: