Person:
Lacadena García-Gallo, Francisco Javier

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First Name
Francisco Javier
Last Name
Lacadena García-Gallo
URI
https://hdl.handle.net/20.500.14352/76233
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Químicas
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
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2020 - 20235
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Start date: 2020 × Item Type: Publication ×

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Now showing 1 - 5 of 5
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    Project number: 350
    EChemTest: sistema de evaluación de la Calidad en Química
    (2022) Sánchez Benítez, Francisco Javier; Díaz Blanco, Cristina; Guerrero Martínez, Andrés; Gutiérrez Alonso, Ángel; Lacadena García-Gallo, Francisco Javier; Lainez Ferrando, Alfredo; Pilo Santos, Miguel; Villalba Díaz, MaríaTeresa; García Linares, Sara
    Este proyecto plantea la herramienta EChemTest como mecanismo de evaluación de la Calidad de un Grado relacionado con la Química. También presenta la oportunidad de evaluar cómo ha influido la docencia online en la adquisición de conocimientos, comparando con cursos anteriores.
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    Nanobody-based EGFR-targeting immunotoxins for colorectal cancer treatment
    (Biomolecules, 2023) Narbona Corral, Javier; Hernández Baraza, Luisa; García Gordo, Rubén; Sanz, Laura; Lacadena García-Gallo, Francisco Javier
    Immunotoxins (ITXs) are chimeric molecules that combine the specificity of a targeting domain, usually derived from an antibody, and the cytotoxic potency of a toxin, leading to the selective death of tumor cells. However, several issues must be addressed and optimized in order to use ITXs as therapeutic tools, such as the selection of a suitable tumor-associated antigen (TAA), high tumor penetration and retention, low kidney elimination, or low immunogenicity of foreign proteins. To this end, we produced and characterized several ITX designs, using a nanobody against EGFR (VHH 7D12) as the targeting domain. First, we generated a nanoITX, combining VHH 7D12 and the fungal ribotoxin α-sarcin (αS) as the toxic moiety (VHHEGFRαS). Then, we incorporated a trimerization domain (TIEXVIII) into the construct, obtaining a trimeric nanoITX (TriVHHEGFRαS). Finally, we designed and characterized a bispecific ITX, combining the VHH 7D12 and the scFv against GPA33 as targeting domains, and a deimmunized (DI) variant of α-sarcin (BsITXαSDI). The results confirm the therapeutic potential of α-sarcin-based nanoITXs. The incorporation of nanobodies as target domains improves their therapeutic use due to their lower molecular size and binding features. The enhanced avidity and toxic load in the trimeric nanoITX and the combination of two different target domains in the bispecific nanoITX allow for increased antitumor effectiveness.
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    A New Optimized Version of a Colorectal Cancer-Targeted Immunotoxin Based on a Non-Immunogenic Variant of the Ribotoxin α-Sarcin
    (Cancers, 2023) Narbona Corral, Javier; García Gordo, Rubén; Tomé Amat, Jaime; Lacadena García-Gallo, Francisco Javier
    Due to its incidence and mortality, cancer remains one of the main risks to human health and lifespans. In order to overcome this worldwide disease, immunotherapy and the therapeutic use of immunotoxins have arisen as promising approaches. However, the immunogenicity of foreign proteins limits the dose of immunotoxins administered, thereby leading to a decrease in its therapeutic benefit. In this study, we designed two different variants of non-immunogenic immunotoxins (IMTXA33αSDI and IMTXA33furαSDI) based on a deimmunized variant of the ribotoxin α-sarcin. The inclusion of a furin cleavage site in IMTXA33furαSDI would allow a more efficient release of the toxic domain to the cytosol. Both immunotoxins were produced and purified in the yeast Pichia pastoris and later functionally characterized (both in vitro and in vivo), and immunogenicity assays were carried out. The results showed that both immunotoxins were functionally active and less immunogenic than the wild-type immunotoxin. In addition, IMTXA33furαSDI showed a more efficient antitumor effect (both in vitro and in vivo) due to the inclusion of the furin linker. These results constituted a step forward in the optimization of immunotoxins with low immunogenicity and enhanced antitumor activity, which can lead to potential better outcomes in cancer treatment.
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    Project number: 150
    EChemTest como herramienta de evaluación en Química
    (2020) Sánchez Benítez, Francisco Javier; Villalba Díaz, Mayte; Lainez Ferrando, Alfredo; Lacadena García-Gallo, Francisco Javier; Gutiérrez Alonso, Ángel; Pilo Santos, Miguel
    El proyecto pretende ser un modelo piloto para su futura implementación como mecanismo de evaluación de Calidad de un Grado relacionado con la Química. La metodología de trabajo pasa por la realización de diferentes pruebas de evaluación (EChemTest) compuestas por preguntas que abarcan todos los temas de la Química General. Estas pruebas se llevan cabo en diferentes momentos del curso académico, incluyendo el inicio y el final del mismo, y pretenden evaluar la adquisición de conocimientos y competencias por parte del alumnado.
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    Der p 1‑based immunotoxin as potential tool for the treatment of dust mite respiratory allergy
    (Scientific Reports, 2020) Lázaro‑Gorines, Rodrigo; López Rodríguez, Juan Carlos; Benedé Pérez, Sara; González, Miguel; Mayorga, Cristobalina; Vogel, Lothar; Martínez Del Pozo, Álvaro; Lacadena García-Gallo, Francisco Javier; Villalba Díaz, María Teresa
    Immunotoxins appear as promising therapeutic molecules, alternative to allergen-specifcimmunotherapy. In this work, we achieved the development of a protein chimera able to promote specifc cell death on efector cells involved in the allergic reaction. Der p 1 allergen was chosen as cell-targeting domain and the powerful ribotoxin α-sarcin as the toxic moiety. The resultant construction, named proDerp1αS, was produced and purifed from the yeast Pichia pastoris. Der p 1-protease activity and α-sarcin ribonucleolytic action were efectively conserved in proDerp1αS. Immunotoxin impact was assayed by using efector cells sensitized with house dust mite-allergic sera. Cell degranulation and death, triggered by proDerp1αS, was exclusively observed on Der p 1 sera sensitized-humRBL-2H3 cells, but not when treated with non-allergic sera. Most notably, equivalent IgE-binding and degranulation were observed with both proDerp1αS construct and native Der p 1 when using purifed basophils from sensitized patients. However, proDerp1αS did not cause any cytotoxic efect on these cells, apparently due to its lack of internalization after their surface IgEbinding, showing the complex in vivo panorama governing allergic reactions. In conclusion, herein we present proDerp1αS as a proof of concept for a potential and alternative new designs of therapeutic tools for allergies. Development of new, and more specifc, second-generation of immunotoxins following proDerp1αS, is further discussed