Construcción de un adenovirus recombinante para la terapia génica del cáncer

Abstract

Despite advances in traditional therapies such as radiotherapy or chemotherapy, no significant improvement has been observed in the survival of cancer patients, which is why different immunotherapy methods based on stimulation of the immune system have been tested so that let him be the one to destroy the tumor. Many of these therapies depend on the activation of T lymphocytes, however, for this to happen, the tumor peptides must be presented in HLA-I molecules, to the cytotoxic T lymphocytes. One of the evasion mechanisms most commonly used by tumors to escape the antitumor immune response is the altered expression of these antigen-presenting molecules on the surface of tumor cells, such that the negative regulation or total loss of the Expression of this molecule on the surface of tumor cells can nullify the clinical effect of immunotherapies based on the activation of T lymphocytes. In this study, recombinant adenoviral genomes for the HLA-A * 02: 01 and HLA- alleles were constructed. B * 44: 02 of the major histocompatibility complex class I in order to generate replication-defective recombinant adenoviruses, by trans-complementation in Ad 293 cells. These adenoviral vectors are proposed as a neoadjuvant gene therapy of immunotherapy against cancer.