Gene therapy for cancer
Gene therapy has recently been shown to be a potential therapeutic alternative for many types of cancer, as well as for the treatment of rare genetic diseases.
Cancer gene therapy
Our research focuses on the development of vectors based on self-replicating RNA derived from alphaviruses to express immunostimulatory molecules locally in tumors. These vectors present several advantages, such as high expression levels, induction of interferon (IFN) type I responses and apoptosis, as well as a high degree of biosafety, since they cannot propagate. In numerous studies we have shown that vectors derived from the alphavirus SFV (Semliki Forest virus) expressing immunostimulatory cytokines, such as interleukin-12 (IL-12), IFNα, or Flt3L (a dendritic cell growth factor) are capable of inducing potent antitumor responses in models of colorectal cancer and hepatocarcinoma, including spontaneous tumors of clinical relevance. We have also shown that the activity of these vectors can be enhanced by combining them with immunomodulatory monoclonal antibodies (MAbs), such as an agonist MAb for CD137, a molecule expressed on the surface of activated T cells, or with MAbs able to block immune checkpoints, such as PD-L1 or PD-1. We are currently evaluating the use of SFV RNA vectors to express these MAbs locally in tumors, which would allow to diminish the toxicity produced by said MAbs when they are administered systemically.
On the other hand, in order to improve SFV vectors, we have developed non-cytopathic variants of them that allow generation of stable cell lines to express therapeutic proteins with potential application in cancer, like immunomodulatory MAbs. We have also recently described that alphaviruses can propagate in the complete absence of their capsid, which has allowed us to develop a new generation of propagative RNA vectors with potential application as oncolytic vectors.
Fecha de actualización: Noviembre 2018