Drug development and new therapies

Immunoregulatory function of T regulatory cells (Treg) may hinder the induction of immune responses against cancer and infectious agents.

FOXP3 transcription factor is essential for the specification and maintenance of Treg cells and it is considered its “master regulator”.

Combination of immunotherapy and virotherapy, using oncolytic viruses, has shown great promise in cancer therapy.

Semliki Forest virus (SFV) vectors are based on a self-replicating RNA that constitutes a promising tool for cancer therapy due to several intrinsic properties that include high expression levels, induction of type I interferon (IFN) responses and apoptosis in tumor cells.

SFV vectors able to express immunostimulatory proteins, such as interleukin-12 (IL-12) or IFNα, have been developed.

• Dravet Syndrome (DS) is a severe encephalopathy characterized by infantile onset, refractory seizures, associated with intellectual, behavioral and motor alterations, as well as increased risk of sudden death. In most cases (~90%), the genetic basis is haploinsufficiency caused by mutations in the SCN1A gene, which encodes a voltage-dependent Na+ channel type 1 (Nav1.1).
• Current anti-epileptic drugs have limited efficacy in DS, despite aggressive combinatorial therapy.
• Due to the complex physiopathology of DS, etiological approaches such as gene therapy have unique chances to obtain a global improvement in the life of these patients.
• Helper-dependent adenovirus vectors (HD-AdV) are very promising tools for therapeutic gene delivery, since they present a high cloning capacity (>30 Kb), and combine long-term expression with high transduction efficiency.

• Introduction:
  Identification of different TCR clonotypes specific for an HLA-A2-restricted epitope of GPC3. Cloning and application of these TCRs in the treatment of hepatocarcinoma.

• Results:
  The developed TCRs recognize and eliminate HLA-A2+GPC3+ tumor cells and have great potential for engineering the patient's autologous T cells to treat GPC3+ tumors.