Advanced Therapies Associated Group

Activity summary

The Advanced Therapies Mixed Unit develops translational research on developing new gene and cell therapies for congenital and acquired diseases with poor prognosis. These include Fanconi anaemia, erythrocyte pyruvate kinase deficiency, and leukocyte adhesion deficiency type I, which are in advanced stages of clinical research with lentiviral vectors developed in the laboratory. Numerous other gene therapies for the treatment of haematological and hepatic diseases, based on the use of lentiviral vectors and gene editing, are in the preclinical research phase. Cell therapies include those based on genetically modified MSCs and those based on regulatory T lymphocytes and CAR-T cells for inflammatory and autoimmune pathologies. New combined immunotherapy protocols are also being developed for the treatment of head and neck squamous cell carcinoma and brain tumours, as well as tumours characterised by gene rearrangements.

Contributions to society

In addition to carrying out clinical trials, the results of which are proving highly satisfactory, pre-clinical studies of new therapeutic developments are also being carried out, which have led to orphan drug designations and international patent applications. We also actively collaborate with patient associations, such as the Fanconi Anaemia Foundation, the Fanconi Anaemia Research Fund, FA Europe and associations for people affected by Blackfan Diamond and pyruvate kinase deficiency in Spain, France, Germany and the USA.

Collaborations

In addition to collaborating with the Center for Biomedical Research Network for Rare Diseases (CIBERER) and the National Network for Advanced Therapies (TERAV), it participates in notable national and international collaborations:

Collaborations with national hospitals for the development of clinical trials: Fundación Jiménez Díaz H. (Dr. José Luis López-Lorenzo); Niño Jesús H., Madrid (Dr. J. Sevilla); Vall d’Hebron H., Barcelona (Dr. C. Díaz de Heredia); Sant Joan de Déu H., Barcelona (Dr. A. Catalá); Gregorio Marañón H. (Dr. C. Beléndez); University Clinic of Navarre (Dr. F. Prosper); Virgen de la Arrixaca H. (Dr. José M. Moraleda, Dr. José Rivera); Salamanca Clinical H. (Dr. Sánchez-Guijo); Jiménez Díaz Foundation (Dr. Pilar Llamas, Dr. García-Olmo); Virgen del Rocío H., Seville (Dr. Salvador Payan).

Collaborations with foreign hospitals for the development of clinical trials: UCL Children’s Hospital (Dr. A. Thrasher); Los Angeles Children’s Hospital (Dr. D. Cohn); Univ. Stanford Children’s Hospital (Dr. M.G. Roncarolo), Chicago Children's Hospital (Dr. Xiao-Nan Li)

National collaborations for preclinical research: Autonomous University of Barcelona and San Pau Hospital, Barcelona (Dr. J. Surrallés); CIMA, Pamplona (Dr. F. Prosper, Dr. Purificación Fortes, Dr. Marta Alonso); Biomedical Research Institute-CSIC-UAM, Madrid (Dr. R. Perona and Dr. Leandro Sastre); Complutense de Madrid University (Dr. Juarranz, Dr. A. Vicente); Gregorio Marañón University Hospital, Madrid (Dr. R. Correa-Rocha and Dr. M. Pion); 12 de Octubre University Hospital (Dr. Joaquín Martínez-López; Dr. Gargini, Dr. Luis Álvarez-Vallina); BloodGenetices (Dr. Mayka Sánchez); ViveBiotech (Dra. Marie Fertin); Pompeu Fabra University (Dr. Marc Güell); Canarias University Hospital, Univ. La Laguna (Dr. Eduardo Salido); Salamanca Clinical Hospital (Dr. Sánchez-Guijo, Dr. Muntion), Niño Jesús H. (Dr. Manuel Ramírez).

International collaborations for preclinical research: Rocket Pharma, USA (Dr. Gaurav Shah); ETH Zurich (Dr. Jacob Corn); Fanconi Anemia Research Foundation (FARF, USA); H. San Louis (Dr. Jean Soulier); Hospital Robert-Debre (Dr. Thierry Leblanc); University Medical Center Freiburg (Dr. Charlotte Niemeyer); SR-TIGET de Milán (Dr. Luigi Naldini; University of Freiburg, Institute for Transfusion Medicine and Gene Therapy (Dr. Toni Cathomen); Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (Dra. Paola Bianchi); Harvard University (Dr. David R. Liu); University of Minnesota (Dr. Branden Moriarity); Fred Hutch Cancer Center (Hans-Peter Kiem); St. Vincent's Institute Fitzroy (Dr. Andrew Deans); Stanford University (Dr. Matthew Porteus); Utrech University Hospital (Dr. Richard van Wijk); Revertium Therapeutics (Dr. Nidhi Jyotsana and Vishal Suri).

PhD Theses

6.6.6-TER AVANZADAS-TESIS

List of publications ordered by publication date

Study of the Effect of Wild-Type and Transiently Expressing CXCR4 and IL-10 Mesenchymal Stromal Cells in a Mouse Model of Peritonitis.

Garcia Gómez-Heras S, Garcia-Arranz M, Vega-Clemente L, Olivera-Salazar R, Vélez Pinto JF, Fernández-García M, Guadalajara H, Yáñez R, Garcia-Olmo D.

Int J Mol Sci. 2023 Dec 30.25(1).

PMID: 38203690

FI: 5,6

Progress and harmonization of gene editing to treat human diseases: Proceeding of COST Action CA21113 GenE-HumDi.

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.

Mol Ther Nucleic Acids. 2023 Dec 12.34:102066.

PMID: 38034032

FI: 8,8

A new age of precision gene therapy.

Schambach A, Buchholz CJ, Torres-Ruiz R, Cichutek K, Morgan M, Trapani I, Büning H.

Lancet. 2023 Nov 22.

PMID: 38006899

FI: 168,9

Detection of the Uveal Melanoma-Associated Mutation GNAQ Q209P from Liquid Biopsy Using CRISPR/Cas12a Technology.

Escalona-Noguero C, Alarcón-Iniesta H, López-Valls M, Del Carpio LP, Piulats JM, Somoza Á, Sot B.

Anal Chem. 2023 Nov 14.95(45):16692-16700.

PMID: 37921444

FI: 7,4

A human genome editing-based MLL::AF4 B-cell ALL model recapitulates key cellular and molecular leukemogenic features.

Bueno C, Torres-Ruíz R, Velasco-Hernandez T, Molina O, Petazzi P, Martinez-Moreno A, Rodríguez-Cortez VC, Vinyoles M, Cantilena S, Williams O, Vega-García N, Rodriguez-Perales S, Segovia JC, Quintana-Bustamante O, Roy A, Meyer C, Marschalek R, Smith A, Milne TA, Fraga MF, Tejedor JRR, Menendez P.

Blood. 2023 Sep 26.

PMID: 37756522

FI: 20,3

Advances and Challenges in the Development of Gene Therapy Medicinal Products for Rare Diseases.

Bueren JA, Auricchio A.

Hum Gene Ther. 2023 Sep.34(17-18):763-775.

PMID: 37694572

FI: 4,2

Soluble mutant huntingtin drives early human pathogenesis in Huntington's disease.

Miguez A, Gomis C, Vila C, Monguió-Tortajada M, Fernández-García S, Bombau G, Galofré M, García-Bravo M, Sanders P, Fernández-Medina H, Poquet B, Salado-Manzano C, Roura S, Alberch J, Segovia JC, Allen ND, Borràs FE, Canals JM.

Cell Mol Life Sci. 2023 Aug 03.80(8):238.

PMID: 37535170

FI: 8

Nanomedical research and development in Spain: improving the treatment of diseases from the nanoscale.

Fernández-Gómez P, Pérez de la Lastra Aranda C, Tosat-Bitrián C, Bueso de Barrio JA, Thompson S, Sot B, Salas G, Somoza Á, Espinosa A, Castellanos M, Palomo V.

Front Bioeng Biotechnol. 2023.11:1191327.

PMID: 37545884

FI: 5,7

MSC therapy ameliorates experimental gouty arthritis hinting an early COX-2 induction.

Medina JP, Bermejo-Álvarez I, Pérez-Baos S, Yáñez R, Fernández-García M, García-Olmo D, Mediero A, Herrero-Beaumont G, Largo R.

Front Immunol. 2023.14:1193179.

PMID: 37533852

FI: 7,3

Expression of HMGCS2 in intestinal epithelial cells is downregulated in inflammatory bowel disease associated with endoplasmic reticulum stress.

Martín-Adrados B, Wculek SK, Fernández-Bravo S, Torres-Ruiz R, Valle-Noguera A, Gomez-Sánchez MJ, Hernández-Walias JC, Ferreira FM, Corraliza AM, Sancho D, Esteban V, Rodriguez-Perales S, Cruz-Adalia A, Nakaya HI, Salas A, Bernardo D, Campos-Martín Y, Martínez-Zamorano E, Muñoz-López D, Gómez Del Moral M, Cubero FJ, Blumberg RS, Martínez-Naves E.

Front Immunol. 2023.14:1185517.

PMID: 37457727

FI: 7,3

Comprehensive characterization of a novel, oncogenic and targetable SEPTIN6::ABL2 fusion in T-ALL.

Lahera A, Vela-Martín L, López-Nieva P, Salgado RN, Rodríguez-Perales S, Torres-Ruiz R, López-Lorenzo JL, Cornago J, Llamas P, Fernández-Navarro P, Sánchez-Domínguez R, Segovia JC, Sastre I, Cobos-Fernández MÁ, Menéndez P, Santos J, Fernández-Piqueras J, Villa-Morales M.

Br J Haematol. 2023 Jun 02.

PMID: 37264982

FI: 6,5

Role of Hospital Exemption in Europe: position paper from the Spanish Advanced Therapy Network (TERAV).

Sánchez-Guijo F, Avendaño-Solá C, Badimón L, Bueren JA, Canals JM, Delgadillo J, Delgado J, Eguizábal C, Fernández-Santos ME, García-Olmo D, González-Aseguinolaza G, Juan M, Martín F, Mata R, Montserrat N, Pérez-Martínez A, Pérez-Simón JA, Prósper F, Urbano-Ispizua Á, Zapata AG, Sureda A, Moraleda JM.

Bone Marrow Transplant. 2023 Jun.58(6):727-728.

PMID: 36966215

FI: 4,8

Specific correction of pyruvate kinase deficiency-causing point mutations by CRISPR/Cas9 and single-stranded oligodeoxynucleotides.

Fañanas-Baquero S, Morín M, Fernández S, Ojeda-Perez I, Dessy-Rodriguez M, Giurgiu M, Bueren JA, Moreno-Pelayo MA, Segovia JC, Quintana-Bustamante O.

Front Genome Ed. 2023.5:1104666.

PMID: 37188156

FI: 0

Gene therapy restores the transcriptional program of hematopoietic stem cells in Fanconi anemia.

Lasaga M, Río P, Vilas-Zornoza A, Planell N, Navarro S, Alignani D, Fernández-Varas B, Mouzo D, Zubicaray J, Pujol RM, Nicoletti E, Schwartz JD, Sevilla J, Ainciburi M, Ullate-Agote A, Surrallés J, Perona R, Sastre L, Prosper F, Gomez-Cabrero D, Bueren JA.

Haematologica. 2023 Apr 06.

PMID: 37021532

FI: 10,1

Access to gene therapy for rare diseases when commercialization is not fit for purpose.

Fox T, Bueren J, Candotti F, Fischer A, Aiuti A, Lankester A, AGORA Initiative, Booth C.

Nat Med. 2023 Mar.29(3):518-519.

PMID: 36782029

FI: 82,9

CRISPR/Cas9-mediated gene editing. A promising strategy in hematological disorders.

Ugalde L, Fañanas S, Torres R, Quintana-Bustamante O, Río P.

Cytotherapy. 2023 Mar.25(3):277-285.

PMID: 36610813

FI: 4,5

Improved efficacy of mesenchymal stromal cells stably expressing CXCR4 and IL-10 in a xenogeneic graft versus host disease mouse model.

Hervás-Salcedo R, Fernández-García M, Hernando-Rodríguez M, Suárez-Cabrera C, Bueren JA, Yáñez RM.

Front Immunol. 2023.14:1062086.

PMID: 36817457

FI: 7,3