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Cancer immunotherapy represents a revolutionary approach harnessing the body’s immune system to eradicate tumor cells. One particularly promising avenue is adoptive cell therapy (ACT), notably CAR-modified T cells, which has revolutionized the landscape of immunotherapies and enhanced patient outcomes.
Inicio - Área Aplicada: Medicina Personalizada - Terapias Avanzadas - Applied Genome Editing for Advanced Therapies | PI: Dr. Karim Benabdellah
Cancer immunotherapy represents a revolutionary approach harnessing the body’s immune system to eradicate tumor cells. One particularly promising avenue is adoptive cell therapy (ACT), notably CAR-modified T cells, which has revolutionized the landscape of immunotherapies and enhanced patient outcomes. However, despite significant strides in CAR-T therapies for certain hematologic diseases, their 87 STRATEGIC PLAN 2024-2027 effectiveness in treating more challenging conditions such as acute myeloid leukemia (AML) and solid tumors remains limited. Due to high immunosuppression of the diseases and the difficulty to obtain enough autologous T cells. To confront these challenges, the research group «Applied Genome Editing for Advanced Therapies (eGATA),» under the leadership of Dr. Karim Benabdellah, aim to increase the efficacy of allogenic CAR-T cell therapy through a multifaceted approach. The group’s robust international collaborations, spearheaded by Dr. Benabdellah’s leadership in the COST action, and close collaboration with Dr. Herrera at Reina Sofia Hospital, serve as pillars for its purpose. Based on this foundation, eGATA encompasses 5 complementary research lines
This research line aims to improve the efficacy of CAR T-cell therapy, particularly in pathologies where these cellular products are not yielding comparable results to Blineage neoplasms, such as AML, MM, and solid tumors. Understanding the cellular and humoral mechanisms governing the TME and its strongly immunosuppressive effects on CAR-T activity is crucial. We are developing combined strategies utilizing genetic engineering and nanoparticles (primarily exosomes and also LNPs) to enhance CAR T-cell therapy effectiveness.
Through this innovative research line, we seek to implement a therapeutic exosome production platform to complement CAR therapy in situations where CAR-T cells alone are ineffective, such as solid tumors and some leukemias. We are improving exosome production in CAR-T cells through genomic manipulation. Our group possesses a range of CRISPR/Cas9-based systems capable of efficiently editing the genome of primary T lymphocytes and various viral systems for overexpression of therapeutic proteins to enhance exosome production efficiency.
In this research line, we are developing CAR-T cells, by the way of gene editing approaches, with additional functionalities by controlling the expression of cytokines with potential to improve efficacy and thus the anti-tumor activity of CAR-T cells. Controlled secretion of these cytokines could enhance the phenotype and potential of edited cells, aiming to improve the efficacy of CAR-T-based therapies. We are developing a PD1-based platform to allow for the expression of cytokine such as IL15 genes, as a proof of concept, to increasing the efficacy, and specificity of fourth-generation CAR-T cells for eliminating CD19+ B neoplasms.
In another line of research, we are exploring the possibility of generating allogeneic CAR-T cells from alternative cellular sources such as umbilical cord blood (CBCD19- CAR-T) and NK cells from various sources (NK-CAR-CD19). We aim to evaluate the potential advantages and disadvantages of different approaches to the use of 88 STRATEGIC PLAN 2024-2027 allogeneic CARs (TCR and/or HLA KO peripheral blood CAR-T cells, NK-CAR, and CBCAR T cells).
Over the past four years, we have generated universal CAR-T cells by eliminating TCR and HLA class II. We have also selected less differentiated universal CAR-T cell populations (TCR KO and HLA KO), thereby enhancing the universal product’s persistence. Our current program aims to improve large-scale cell cultures to expand and freeze double KO universal cells with a well-defined phenotype, facilitating the initiation of a clinical trial in Andalusia with CD19-CART universal DKO T cells.
Our research introduces a highly novel and pioneering approach that sets it apart in the field of cancer immunotherapy. The integration of gene editing, targeted delivery of therapeutic nanoparticles (LNPs), represents an unprecedented and cutting-edge strategy. This innovative combination of techniques aims to overcome the challenges of immune evasion, immunosuppression, and antigen targeting that have limited the efficacy of current CAR-T cell therapies in AML and solid tumours.
CAR- T-cell immunotherapy has changed the probability of survival of patients with B cell hematologic neoplasms in advanced stages. Huge efforts worldwide are currently trying to expand this success to other hematologic neoplasms mainly AML as well as solid tumors. If we associate the ability to mitigate immunosuppression with the use of allogeneic CAR-T cells as we propose we will be overcoming the two main obstacles to the use of CAR-T therapy in patients with relapsed or refractory oncologic diseases in whom there is no therapy that offers a real chance of survival in the medium term.
Establishing strong European collaboration through the COST action that we are leading, as well as through the creation of EBTs based on the emerging knowledge from our research team.
Entidad concedente: SUBVENCIONES PARA LA FINANCIACION DE LA I+D+i EN BIOMEDICINA Y EN CIENCIAS DE LA SALUD EN ANDALUCÍA consejería de salud y familia
Entidad concedente: PAIDI 2020 – AYUDAS A PROYECTOS DE INVESTIGACIÓN PARA LOS
AGENTES DEL SISTEMA ANDALUZ DEL CONOCIMIENTO 2021. CONSEJERÍA DE UNIVERSIDAD, INVESTIGACIÓN E INNOVACIÓN
Autores: Berggreen AH, Petersen JL, Lin L, Benabdellah K, Luo Y
09/2023 - Journal of extracellular biology
Autores: Pavlovic K, Carmona-Luque M, Corsi GI, Maldonado-Pérez N, Molina-Estevez FJ, Peralbo-Santaella E, Cortijo-Gutiérrez M, Justicia-Lirio P, Tristán-Manzano M, Ronco-Díaz V, Ballesteros-Ribelles A, Millán-López A, Heredia-Velázquez P, Fuster-García C, Cathomen T, Seemann SE, Gorodkin J, Martin F, Herrera C, Benabdellah K
05/2024 - Frontiers in immunology
Autores: Blaya-Cánovas JL, Griñán-Lisón C, Blancas I, Marchal JA, Ramírez-Tortosa C, López-Tejada A, Benabdellah K, Cortijo-Gutiérrez M, Cano-Cortés MV, Graván P, Navarro-Marchal SA, Gómez-Morales J, Delgado-Almenta V, Calahorra J, Agudo-Lera M, Sagarzazu A, Rodríguez-González CJ, Gallart-Aragón T, Eich C, Sánchez-Martín RM, Granados-Principal S
05/2024 - Molecular cancer
Autores: Fakhkhari M, Salih I, Maazaz N, Nembaware V, Munung NS, Matimba A, Chala S, Belmouden A, Chappell K, Mutesa L, El-Kamah G, Oumzil H, Baassi L, Abbas Y, Alimohamed MZ, Ramsay M, Williams S, Benabdellah K, Idaghdour Y, Wonkam A, Sadki K
05/2024 - The American journal of tropical medicine and hygiene
Autores: Cavazza A, Hendel A, Bak RO, Rio P, Güell M, Lainšček D, Arechavala-Gomeza V, Peng L, Hapil FZ, Harvey J, Ortega FG, Gonzalez-Martinez C, Lederer CW, Mikkelsen K, Gasiunas G, Kalter N, Gonçalves MAFV, Petersen J, Garanto A, Montoliu L, Maresca M, Seemann SE, Gorodkin J, Mazini L, Sanchez R, Rodriguez-Madoz JR, Maldonado-Pérez N, Laura T, Schmueck-Henneresse M, Maccalli C, Grünewald J, Carmona G, Kachamakova-Trojanowska N, Miccio A, Martin F, Turchiano G, Cathomen T, Luo Y, Tsai SQ, Benabdellah K, COST Action CA21113
10/2023 - Molecular therapy. Nucleic acids
Autores: Olaechea A, Benabdellah K, Vergara-Buenaventura A, Gómez-Melero S, Cafferata EA, Meza-Mauricio J, Padial-Molina M, Galindo-Moreno P
12/2023 - Stem cells translational medicine
Autores: Zvintzou E, Xepapadaki E, Skroubis G, Mparnia V, Giannatou K, Benabdellah K, Kypreos KE
06/2023 - Pharmaceuticals (Basel, Switzerland)
Autores: Atilla E, Benabdellah K
05/2023 - Cancers
Autores: Tristán-Manzano M, Maldonado-Pérez N, Justicia-Lirio P, Cortijo-Gutierréz M, Tristán-Ramos P, Blanco-Benítez C, Pavlovic K, Aguilar-González A, Muñoz P, Molina-Estevez FJ, Griesche V, Marchal JA, Heras SR, Benabdellah K, Martin F
03/2023 - Molecular therapy. Nucleic acids
Autores: Aparicio-Pérez C, Carmona M, Benabdellah K, Herrera C
04/2023 - Frontiers in immunology
Autores: Diaz-Ruano AB, Martinez-Alarcon N, Perán M, Benabdellah K, Garcia-Martinez MLÁ, Preda O, Ramirez-Tortosa C, Gonzalez-Hernandez A, Marchal JA, Picon-Ruiz M
01/2023 - International journal of molecular sciences
Autores: Maldonado-Pérez N, Tristán-Manzano M, Justicia-Lirio P, Martínez-Planes E, Muñoz P, Pavlovic K, Cortijo-Gutiérrez M, Blanco-Benítez C, Castella M, Juan M, Wenes M, Romero P, Molina-Estévez FJ, Marañón C, Herrera C, Benabdellah K, Martin F
10/2022 - Frontiers in immunology
Autores: Tristán-Manzano M, Maldonado-Pérez N, Justicia-Lirio P, Muñoz P, Cortijo-Gutiérrez M, Pavlovic K, Jiménez-Moreno R, Nogueras S, Carmona MD, Sánchez-Hernández S, Aguilar-González A, Castella M, Juan M, Marañón C, Marchal JA, Benabdellah K, Herrera C, Martin F
07/2022 - Molecular therapy oncolytics
Autores: Cueto-Ureña C, Mocholí E, Escrivá-Fernández J, González-Granero S, Sánchez-Hernández S, Solana-Orts A, Ballester-Lurbe B, Benabdellah K, Guasch RM, García-Verdugo JM, Martín F, Coffer PJ, Pérez-Roger I, Poch E
06/2022 - Frontiers in cell and developmental biology
Autores: Tristán-Manzano M, Maldonado-Pérez N, Justicia-Lirio P, Muñoz P, Cortijo-Gutiérrez M, Pavlovic K, Jiménez-Moreno R, Nogueras S, Carmona MD, Sánchez-Hernández S, Aguilar-González A, Castella M, Juan M, Marañón C, Marchal JA, Benabdellah K, Herrera C, Martin F
05/2022 - Molecular therapy oncolytics
Autores: Kröger N, Gribben J, Chabannon C, Yakoub-Agha I, Einsele H, Benabdellah K, Thomas S, Abken H
02/2022 -
Autores: Gutierrez-Guerrero A, Abrey Recalde MJ, Mangeot PE, Costa C, Bernadin O, Périan S, Fusil F, Froment G, Martinez-Turtos A, Krug A, Martin F, Benabdellah K, Ricci EP, Giovannozzi S, Gijsbers R, Ayuso E, Cosset FL, Verhoeyen E
02/2021 - Frontiers in genome editing
Autores: Cortijo-Gutiérrez M, Sánchez-Hernández S, Tristán-Manzano M, Maldonado-Pérez N, Lopez-Onieva L, Real PJ, Herrera C, Marchal JA, Martin F, Benabdellah K
08/2021 - Pharmaceutics
Autores: Aheget H, Mazini L, Martin F, Belqat B, Marchal JA, Benabdellah K
12/2020 - Cancers
Autores: Pavlovic K, Tristán-Manzano M, Maldonado-Pérez N, Cortijo-Gutierrez M, Sánchez-Hernández S, Justicia-Lirio P, Carmona MD, Herrera C, Martin F, Benabdellah K
09/2020 - Frontiers in immunology
Autores: Tristán-Manzano M, Justicia-Lirio P, Maldonado-Pérez N, Cortijo-Gutiérrez M, Benabdellah K, Martin F
09/2020 - Frontiers in immunology
Autores: Aheget H, Tristán-Manzano M, Mazini L, Cortijo-Gutierrez M, Galindo-Moreno P, Herrera C, Martin F, Marchal JA, Benabdellah K
07/2020 - Journal of clinical medicine
Autores: Sánchez-Hernández S, Aguilar-González A, Guijarro-Albaladejo B, Maldonado-Pérez N, Ramos-Hernández I, Cortijo-Gutiérrez M, Sánchez Martín RM, Benabdellah K, Martin F
06/2020 - Cells
Autores: Benabdellah K, Sánchez-Hernández S, Aguilar-González A, Maldonado-Pérez N, Gutierrez-Guerrero A, Cortijo-Gutierrez M, Ramos-Hernández I, Tristán-Manzano M, Galindo-Moreno P, Herrera C, Martin F
06/2020 - Stem cells translational medicine
Autores: Gómez-Gallego T, Benabdellah K, Merlos MA, Jiménez-Jiménez AM, Alcon C, Berthomieu P, Ferrol N
05/2019 - Frontiers in plant science
Autores: Martín F, Tristán-Manzano M, Maldonado-Pérez N, Sánchez-Hernández S, Benabdellah K, Cobo M
01/2019 - Methods in molecular biology (Clifton, N.J.)
Autores: Sánchez-Hernández S, Gutierrez-Guerrero A, Martín-Guerra R, Cortijo-Gutierrez M, Tristán-Manzano M, Rodriguez-Perales S, Sanchez L, Garcia-Perez JL, Chato-Astrain J, Fernandez-Valades R, Carrillo-Galvez AB, Anderson P, Montes R, Real PJ, Martin F, Benabdellah K
12/2018 - Molecular therapy. Nucleic acids
Autores: Gutierrez-Guerrero A, Sanchez-Hernandez S, Galvani G, Pinedo-Gomez J, Martin-Guerra R, Sanchez-Gilabert A, Aguilar-González A, Cobo M, Gregory P, Holmes M, Benabdellah K, Martin F
03/2018 - Human gene therapy
Autores: Marin-Bañasco C, Benabdellah K, Melero-Jerez C, Oliver B, Pinto-Medel MJ, Hurtado-Guerrero I, de Castro F, Clemente D, Fernández O, Martin F, Leyva L, Suardíaz M
02/2017 - British journal of pharmacology
Autores: Benabdellah K, Muñoz P, Cobo M, Gutierrez-Guerrero A, Sánchez-Hernández S, Garcia-Perez A, Anderson P, Carrillo-Gálvez AB, Toscano MG, Martin F
11/2016 - Scientific reports
Autores: Martin F, Sánchez-Hernández S, Gutiérrez-Guerrero A, Pinedo-Gomez J, Benabdellah K
09/2016 - International journal of molecular sciences
Autores: Barriocanal-Casado E, Cueto-Ureña C, Benabdellah K, Gutiérrez-Guerrero A, Cobo M, Hidalgo-Gutiérrez A, Rodríguez-Sevilla JJ, Martín F, López LC
06/2016 - PloS one
Autores: Tamayo E, Benabdellah K, Ferrol N
02/2016 - PloS one
Autores: Toscano MG, Muñoz P, Sánchez-Gilabert A, Cobo M, Benabdellah K, Anderson P, Ramos-Mejía V, Real PJ, Neth O, Molinos-Quintana A, Gregory PD, Holmes MC, Martin F
02/2016 - Molecular therapy : the journal of the American Society of Gene Therapy
Autores: Carrillo-Galvez AB, Cobo M, Cuevas-Ocaña S, Gutiérrez-Guerrero A, Sánchez-Gilabert A, Bongarzone P, García-Pérez A, Muñoz P, Benabdellah K, Toscano MG, Martín F, Anderson P
01/2015 - Stem cells (Dayton, Ohio)
Autores: Benabdellah K, Gutierrez-Guerrero A, Cobo M, Muñoz P, Martín F
01/2014 - PloS one
Autores: Toscano MG, Anderson P, Muñoz P, Lucena G, Cobo M, Benabdellah K, Gregory PD, Holmes MC, Martin F
03/2013 - Disease models & mechanisms
Autores: Cobo M, Anderson P, Benabdellah K, Toscano MG, Muñoz P, García-Pérez A, Gutierrez I, Delgado M, Martin F
01/2013 - Cell transplantation
Autores: Muñoz P, Toscano MG, Real PJ, Benabdellah K, Cobo M, Bueno C, Ramos-Mejía V, Menendez P, Anderson P, Martín F
01/2012 - PloS one
Autores: Ienne S, Pappas G Jr, Benabdellah K, González A, Zingales B
04/2012 - Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
Autores: Tisserant E, Kohler A, Dozolme-Seddas P, Balestrini R, Benabdellah K, Colard A, Croll D, Da Silva C, Gomez SK, Koul R, Ferrol N, Fiorilli V, Formey D, Franken P, Helber N, Hijri M, Lanfranco L, Lindquist E, Liu Y, Malbreil M, Morin E, Poulain J, Shapiro H, van Tuinen D, Waschke A, Azcón-Aguilar C, Bécard G, Bonfante P, Harrison MJ, Küster H, Lammers P, Paszkowski U, Requena N, Rensing SA, Roux C, Sanders IR, Shachar-Hill Y, Tuskan G, Young JPW, Gianinazzi-Pearson V, Martin F
02/2012 - The New phytologist
Autores: Benabdellah K, Cobo M, Muñoz P, Toscano MG, Martin F
01/2011 - PloS one
Autores: Toscano MG, Romero Z, Muñoz P, Cobo M, Benabdellah K, Martin F
02/2011 - Gene therapy
Autores: González-Guerrero M, Oger E, Benabdellah K, Azcón-Aguilar C, Lanfranco L, Ferrol N
06/2010 - Current genetics
Autores: González-Guerrero M, Benabdellah K, Valderas A, Azcón-Aguilar C, Ferrol N
02/2010 - Mycorrhiza
Autores: Benabdellah K, Azcón-Aguilar C, Valderas A, Speziga D, Fitzpatrick TB, Ferrol N
11/2009 - The New phytologist
Autores: Toscano MG, Benabdellah K, Muñoz P, Frecha C, Cobo M, Martín F
11/2009 - Human gene therapy
Autores: Benabdellah K, Ruiz-Lozano JM, Aroca R
08/2009 - Plant molecular biology
Autores: Benabdellah K, Merlos MA, Azcón-Aguilar C, Ferrol N
01/2009 - Fungal genetics and biology : FG & B
Autores: Delgado M, Toscano MG, Benabdellah K, Cobo M, O'Valle F, Gonzalez-Rey E, Martín F
04/2008 - Arthritis and rheumatism
Autores: Toscano MG, Frecha C, Benabdellah K, Cobo M, Blundell M, Thrasher AJ, García-Olivares E, Molina IJ, Martin F
02/2008 - Human gene therapy
Autores: Benabdellah K, González-Rey E, González A
09/2007 - Molecular microbiology
Autores: Pappas GJ Jr, Benabdellah K, Zingales B, González A
08/2005 - Molecular and biochemical parasitology
Autores: Benabdellah K, Azcón-Aguilar C, Ferrol N
04/2000 - Journal of experimental botany
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