DSpace Collection:
https://hdl.handle.net/10171/63710
2024-03-28T16:58:27ZOmalizumab, the innovative biologic that disrupted the market of the treatment of allergic diseases
https://hdl.handle.net/10171/66799
Title: Omalizumab, the innovative biologic that disrupted the market of the treatment of allergic diseases
Abstract: Omalizumab, the blockbuster monoclonal antibody anti-IgE that revolutionized the market by
the disruptive innovation that supposed more than 20 years ago. This biological drug changed
the paradigm of the treatment of allergic diseases, particularly severe allergic asthma and
chronic spontaneous urticaria. It opened up a new alternative world of possible treatments,
covering the clinical unmet needs of asthmatic patients and creating value for patients who do
not respond well to traditional medicines (small-molecules). Its efficacy and safety have been
demonstrated in numerous clinical trials and Real-World Evidence. These observations have
favoured the life cycle management of the product for new applications, including nasal
polyposis and food allergies. However, it is no longer the only biological on the market for the
treatment of these pathologies, so how is it possible that after so many years it is still a blue
ocean product?2022-01-01T00:00:00ZCharacterization of potential therapeutic targets in Leishmania infantum
https://hdl.handle.net/10171/66798
Title: Characterization of potential therapeutic targets in Leishmania infantum
Abstract: Leishmaniasis is a parasitic disease caused by various species of Leishmania, which affects
millions of people worldwide. Current treatments for leishmaniasis often present adverse
effects and may not be effective against every Leishmania strain or form of the disease.
Therefore, it is essential to explore new therapeutic approaches to combat the parasite. In this
study, we focused on the PeBoW complex proteins homologous in Leishmania, which is
involved in ribosomal biogenesis and plays a critical role in cancer development in mammalian
cells. Recently, a homologue of the oncogene PES1 was found in Leishmania major, which
plays a crucial role in parasite infectivity. Given this, we analyzed the possibility of using other
PeBoW complex partner genes in Leishmania as therapeutic targets for leishmaniasis treatment.
Specifically, our investigation aimed to characterize the partner WDR12 homologous in
Leishmania infantum (LmjWDR12) as new therapeutic approach.2023-01-01T00:00:00ZDevelopment of G9a-targeted BioPROTACs based on peptides and nanobodies
https://hdl.handle.net/10171/66794
Title: Development of G9a-targeted BioPROTACs based on peptides and nanobodies
Abstract: This project arose motivated by the high incidence that neoplastic pathologies have nowadays,
and therefore by the need that our society has to find a solution against them. The main objective
of this research was to identify specific peptides and nanobodies against G9a methyltransferase,
whose role in cancer is to introduce epigenetic modifications to silence tumor suppressor genes.
The strategy followed focuses on degrading this enzyme through the Biological Proteolysis
Targeting Chimera (BioPROTAC) system, made up of either the aforementioned peptides or
nanobodies. A search for these specific molecules was carried out using phage display, to find
the most specific candidates against the previously produced and purified G9a. Later, the
binding affinity of the selected clones was evaluated, the BioPROTAC construct was designed,
and immunocytochemistry (ICQ) was performed to check their cellular internalization. In short,
it was possible to select 3 peptide clones and 16 nanobodies with a good affinity for G9a, in
addition to designing a system capable of being introduced into the tumor cell. This represents
a project of Targeted Protein Degradation (TPD) for drug discovery with its main objectives
met. Furthermore, this study will facilitate future investigations aimed at confirming the
efficacy of the system to degrade the enzyme, in order to conduct additional testing of its
therapeutic effect.2022-01-01T00:00:00ZDesarrollo de un método de cribado de fármacos para identificar nuevas drogas capaces de revertir el fenotipo resistente de las células cancerosas a la destrucción por células CAR-T.
https://hdl.handle.net/10171/66793
Title: Desarrollo de un método de cribado de fármacos para identificar nuevas drogas capaces de revertir el fenotipo resistente de las células cancerosas a la destrucción por células CAR-T.
Abstract: En los últimos años, la terapia de células T con receptor de antígeno quimérico (CAR) se
ha convertido en un tratamiento prometedor para el tratamiento del cáncer. A pesar de
este progreso, una proporción significativa de pacientes experimenta resistencia a la
terapia CAR-T. Las células cancerosas pueden ser insensibles a la destrucción por las
células CAR-T, lo que se conoce como resistencia intrínseca. Esta resistencia intrínseca
es responsable de una parte muy significativa del fracaso de este tipo de terapias que
afecta a todo tipo de tumores, siendo una dificultad adicional para la eficacia de las células
CAR-T en el tratamiento de tumores sólidos. Mucho de los mecanismos de resistencia
intrínseca están regulados a nivel epigenético. Recientemente, se han desarrollado y
probado varios inhibidores epigenéticos en cáncer. El enfoque principal de la mayoría de
los estudios hasta ahora ha sido el efecto citotóxico directo de estos compuestos, y pocos
estudios han investigado la capacidad de revertir el fenotipo resistente de las células
cancerosas a la terapia CAR-T. Existe la necesidad de una metodología sistemática para
identificar nuevas drogas que sensibilicen a la célula tumoral a la destrucción por las
células CAR-T. Mediante la expresión de flaying luciferase (fLuc) en líneas murinas de
tumores sólidos que expresan el antígeno EGFRvIII, hemos establecido un protocolo
simple, preciso, sensible y robusto para detectar sensibilizadores epigenéticos.
Demostramos la eficacia de nuestro protocolo e identificamos varios inhibidores
epigenéticos capaces de sensibilizar a las células tumorales a la destrucción por un CAR
anti-EGFRvIII.2023-01-01T00:00:00Z