Drug development and new therapies

"We research in those therapeutic areas that can provide new pharmacological treatments for our patients."
ANTONIO PINEDA-LUCENA
DIRECTOR OF TRANSLATIONAL RESEARCH

We are advancing in the knowledge of new therapeutic strategies

From discovery to actual application in the treatment of patients' diseases, our research culminates in the development of new therapies, drugs and diagnostic tools.

  • Glypican 3 specific T cell receptors for adoptive T cell therapy

    Target: GPC3

    Therapies based on the adoptive cell transfer of genetically modified T cells with tumor-specific T-cell receptors (TCRs) hold great promise for the treatment of solid cancer, as TCRs can cover a wide range of target antigens including tumor-associated antigens(TAA) and those derived from individual patient somatic mutations. In this context:

    • TCR-therapy targeting shared TAA may be easily exploited in cancer immunotherapy. However, TAA-specific high-affinity TCRs are not readily available directly from human immune repertoires, as central tolerance mechanisms have depleted T cells with high-affinity TCRs for self-epitopes.
    • Transgenic mice expressing HLA molecules are an excellent source of high-affinity TCRs against TAA, since mice lack tolerance for human antigens.
    • Using HLA–transgenic mice, high-affinity TCRs to TAA have been developed and these murine TCRs have shown effective anti-tumor response in clinical trials.
    • Glypican-3 (GPC3) is an interesting TAA for adoptive T cell therapy since it is undetectable in normal adult tissue but is strongly expressed in certain tumors.

    Indication: Hepatocellular carcinoma, ovarian clear cell carcinoma, melanoma, squamous cell carcinoma of the lung, hepatoblastoma, Wilms tumor, yolk sac tumors, among others.

    • Keywords:
    • Cáncer
    • ,
    • Terapia celular
    • Early Discovery
    • Discovery
    • Preclinical
    • Clinical
    • Diagnostics
  • CM-1315-P60. Inhibitors of FOXP3 transcription factor for cancer therapy

    Target: Disruption of FOXP3 dimerization

    • Although Treg are essential for the prevention of autoimmune diseases, their immunoregulatory function 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 thus, it is considered as the “master regulator” of Treg cells.
    • Development of inhibitors of FOXP3 might give new therapeutic opportunities for these diseases.
    • We identified a peptide (named P60) able to enter into the cells, bind to FOXP3, and impair Treg activity in vitro and in vivo (Patent ES2328776, WO2009065982).
    • P60 binds to the intermediate region of FOXP3 and inhibits its homodimerization and interaction with the transcription factor AML1/Runx1.
    • Characterization has been performed to identify those residues which contribute to the stability of P60-FOXP3 interactions. Combinatorial mutation analysis has allowed us to identify P60-derived peptides with higher Foxp3 binding affinity and stronger biological and antitumoral activity than the original P60.

    • Keywords:
    • Cáncer
    • ,
    • Infecciones crónicas virales
    • ,
    • Inmunoterapia
    • ,
    • Inmunorregulación
    • Early Discovery
    • Discovery
    • Preclinical
    • Clinical
    • Diagnostics
  • FOXP3. Inhibitors of FOXP3 Transcription Factor for cancer therapy

    Target: Disruption of FOXP3 dimerization

    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”.

    • Keywords:
    • Inmunoterapia
    • ,
    • Cáncer
    • ,
    • Inmunorregulación
    • Early Discovery
    • Discovery
    • Preclinical
    • Clinical
    • Diagnostics
  • Cancer ViroTherapy. Semliki Forest Virus: An efficient self-replicative RNA vector for cancer therapy

    Target: Inmune response

    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.

    • Keywords:
    • Inmunoterapia
    • ,
    • Cáncer
    • ,
    • Virus Oncolíticos
    • ,
    • Semliki Forest Virus
    • Early Discovery
    • Discovery
    • Preclinical
    • Clinical
    • Diagnostics