Luis Álvarez-Vallina, H12O-CNIO Cancer Immunotherapy Clinical Research Unit. EuroMAbNet

Members

Luis Álvarez-Vallina

Name of the laboratory

H12O-CNIO Cancer Immunotherapy Clinical Research Unit: Clinical Research Programme; Spanish National Cancer Research Centre (CNIO); Calle Melchor Fernández Almagro 3; 28029 Madrid, Spain; +34 912 246 900

Cancer Immunotherapy Unit / Unidad de Inmunoterapia del Cáncer (UNICA): Hospital Universitario 12 de Octubre; Avda. de Córdoba, s/n; 28041 Madrid, Spain; +34 9177927730; Web

Members of the laboratory

Members: H12O-CNIO Cancer Immunotherapy Clinical Research Unit

Unit Leader: Luis Álvarez-Vallina lalvarezv@ext.cnio.es lav.imas12@h12o.es
Senior Research Associates: Belén Blanco Durango bblanco.imas12@h12o.es; Anaïs Jiménez-Reinoso anjimenez@ext.cnio.es
Post-Doctoral Fellows: Rodrigo Lázaro Gorines rlazaro@ext.cnio.es; Antonio Tapia Galisteo atapia@ext.cnio.es; Ivana Zagorac izagorac@ext.cnio.es
PhD Students: Carmen Domínguez Alonso cdominguez.imas12@h12o.es; Francisco Javier Arroyo farroyor@salud.madrid.org; Laura Rubio Pérez laura.rubio.imas12@h12o.es; Marina Gómez Rosel marinagomezrosel.imas12@h12o.es; Eva García Veros egarciav@ext.cnio.es; Alejandro Segura Tudela alejandro.segura@salud.madrid.org; Miriam Velasco Sidro miriam.velasco@salud.madrid.org
Technicians: Yedra Pacheco mpacheco@ext.cnio.es

Research activities

Our Unit focuses on understanding the molecular and cellular mechanisms of cancer immune escape for designing next-generation cancer immunotherapies. For example, we have developed a novel cancer immunotherapy strategy based on the secretion of bispecific T cell-engaging (TCE) antibodies by engineered human T (STAb-T) cells, which has been shown to be effective in solid and hematological malignancies and is currently in clinical trial.

The Cancer Immunotherapy Clinical Research Unit has several research areas of interest:

Reactivation of pre-existing tumor-specific endogenous T cell repertoires using immunomodulatory bispecific antibodies
Development of T cell redirecting strategies to improve the clinical efficacy and safety profile of tumor-reactive artificial T cells.
Development of multi-targeting approaches recognizing tumor-associated antigens (TAA) and/or tumor-specific antigens (TSA) at both extra- and intracellular locations.
Generation of multivalent and multispecific antibody formats and the use of engineered mRNA-based gene delivery systems.

Techniques available

Antibody Engineering and formating
Generation of multispecific immunomodulatory antibodies
Mammalian expresión
Antibody characterization
In vivo expression of bispecific antibodies using lentivirus and nucleoside-modified messenger RNA (modRNA)
Lymphocyte engineering with antibody-based molecules: chimeric antigen receptors (CAR-T cells) and/or bispecific T cell-engaging (TCE) antibodies (STAb-T cells)

Publications (2019-present)

Rubio-Pérez L, Lázaro-Gorines R, Harwood SL, Compte M, Navarro R, Tapia-Galisteo A, Bonet J, Blanco B, Lykkemark S, Ramírez-Fernández Á, Ferreras-Gutiérrez M, Domínguez-Alonso C, Díez-Alonso L, Segura-Tudela A, Hangiu O, Erce-Llamazares A, Blanco FJ, Santos C, Rodríguez-Peralto JL, Sanz L, Álvarez-Vallina L. A PD-L1/EGFR bispecific antibody combines immune checkpoint blockade and direct anti-cancer action for an enhanced anti-tumor response. Oncoimmunology. (2023) 12:2205336.
Tapia-Galisteo A, Compte M, Álvarez-Vallina L, Sanz L. When three is not a crowd: trispecific antibodies for enhanced cancer cancer immunotherapy. Theranostics (2023)13:1028-1041.
Jiménez-Reinoso A, Tirado N, Martinez-Moreno A, Díaz VM, García-Peydró M, Hangiu O, Díez-Alonso L, Albitre Á, Penela P, Toribio ML, Menéndez P, Álvarez-Vallina L, Sánchez Martínez D. Efficient preclinical treatment of cortical T cell acute lymphoblastic leukemia with T lymphocytes secreting anti-CD1a T cell engagers. J Immunother Cancer (2022) 10:e005333.
Blanco B,Ramírez-Fernández A, Bueno C, Argemí-Muntadas A, Fuentes P, Aguilar-Sopeña O, Gutierrez-Agüera F, Romina Zanetti S, Tapia-Galisteo A, Díez-Alonso L, Segura-Tudela A, Castellà M, Marzal B, Betriu S, Harwood SL, Compte C, Lykkemark S, Erce-Llamazares A, Rubio-Pérez L, Jiménez-Reinoso A, Domínguez-Alonso C, Neves M, Morales P, Paz-Artal E, Guedan S, Sanz L, Toribio ML, Roda-Navarro P, Juan M, Menéndez P, Álvarez-Vallina L. Overcoming CAR-mediated CD19 downmodulation and leukemia relapse with T lymphocytes secreting anti-CD19 T cell engagers. Cancer Immunol Res. (2022) 10:498-511.
Hangiu O, Compte M, Dinesen A, Navarro R, Tapia-Galisteo A, Mandrup OA, Erce-Llamazares A, Lázaro-Gorines R, Nehme-Álvarez D, Domínguez-Alonso C, Harwood SL, Alfonso C, Blanco B, Rubio-Pérez L, Jiménez-Reinoso A, Díez-Alonso L, Blanco FJ, Sanz L, Howard KA, Álvarez-Vallina L. Tumor targeted 4-1BB agonist antibody-albumin fusions with high affinity to FcRn induce anti-tumor immunity without toxicity. iScience (2022) 25:104958.
Ramírez-Fernández A, Aguilar-Sopeña O, Díez-Alonso L, Segura-Tudela A, Domínguez-Alonso C, Álvarez-Vallina L, Blanco B. Synapse topology and downmodulation events are determinant for the functional outcome of anti-CD19 T cell-redirecting strategies. Oncoimmunology. (2022) 11:2054106.
Tapia-Galisteo A, Sánchez-Rodríguez I, Aguilar-Sopeña O, Harwood SL, Navarro R, Martín-García L, Gutiérrez F, Corbacho C, Compte M, Blanco FJ, Chames P, Roda-Navarro P, Álvarez-Vallina L, Sanz L. Trispecific T-cell engagers for dual tumor-targeting of colorectal cancer Oncoimmunology. (2022) 11:2034355.
Compte M, Harwood SL, Erce-Llamazares A, Tapia-Galisteo A, Romero E, Ferrer I, Garrido-Martin EM, Enguita AB, Ochoa MC, Blanco B, Oteo M, Merino N, Nehme-Álvarez D, Hangiu O, Domínguez-Alonso C, Zonca M, Ramírez-Fernández A, Blanco FJ, Morcillo MA, Muñoz IG, Melero I, Rodriguez-Peralto JL, Paz-Ares L, Sanz L, Alvarez-Vallina L. An Fc-free EGFR-specific 4-1BB-agonistic Trimerbody Displays Broad Antitumor Activity in Humanized Murine Cancer Models without Toxicity. Clin Cancer Res. (2021) 27:3167-3177.
Compte M, Harwood SL, Martínez-Torrecuadrada J, Perez-Chacon G, González-García P, Tapia-Galisteo A, Van Bergen En Henegouwen PMP, Sánchez A, Fabregat I, Sanz L, Zapata JM, Alvarez-Vallina L. Case Report: An EGFR-Targeted 4-1BB-agonistic Trimerbody Does Not Induce Hepatotoxicity in Transgenic Mice With Liver Expression of Human EGFR. Front Immunol. (2021) 11:614363.
Sanz L, Álvarez-Vallina L. Engineered mRNA and the Rise of Next-Generation Antibodies. Antibodies (2021) 10:37.
Rousso-Noori L, Mastandrea I, Talmor S, Waks D, Globerson-Levin A, Haugas M, Teesalu T, Alvarez-Vallina L, Eshhar Z, Friedmann-Morvinski D. P32, a novel CAR T cell target with dual antitumor and antiangiogenic therapeutic potential in gliomas. Nat Commun. (2021) 12:3615.
Blanco B, Domínguez-Alonso C, Alvarez-Vallina L. Bispecific Immunomodulatory Antibodies for Cancer Immunotherapy. Clin Cancer Res. (2021) 27:5457-5464.
Mandrup OA, Ong SC, Lykkemark S, Dinesen A, Rudnik-Jansen I, Dagnæs-Hansen NF, Andersen JT, Alvarez-Vallina L, Howard KA. Programmable half-life and anti-tumour effects of bispecific T-cell engager-albumin fusions with tuned FcRn affinity. Commun Biol. (2021) 4:310.
Jiménez-Reinoso A, Nehme-Álvarez D, Domínguez-Alonso C, Álvarez-Vallina L. Synthetic TILs: Engineered Tumor-Infiltrating Lymphocytes With Improved Therapeutic Potential. Front Oncol. (2021) 10:593848.
Navarro R, Tapia-Galisteo A, Martín-García L, Tarín C, Corbacho C, Gómez-López G, Sánchez-Tirado E, Campuzano S, González-Cortés A, Yáñez-Sedeño P, Compte M, Álvarez-Vallina L, Sanz L. TGF-β-induced IGFBP-3 is a key paracrine factor from activated pericytes that promotes colorectal cancer cell migration and invasion. Mol Oncol. (2020) 14:2609-2628.
Blanco B, Ramírez-Fernández Á, Alvarez-Vallina L. Engineering Immune Cells for in vivo Secretion of Tumor-Specific T Cell-Redirecting Bispecific Antibodies. Front Immunol. (2020) 11:1792.
Roda-Navarro P, Álvarez-Vallina L. Understanding the Spatial Topology of Artificial Immunological Synapses Assembled in T Cell-Redirecting Strategies: A Major Issue in Cancer Immunotherapy. Front Cell Dev Biol. (2020) 7:370.
Soldevilla B, Carretero-Puche C, Gomez-Lopez G, Al-Shahrour F, Riesco MC, Gil-Calderon B, Alvarez-Vallina L, Espinosa-Olarte P, Gomez-Esteves G, Rubio-Cuesta B, Sarmentero J, La Salvia A, Garcia-Carbonero R. The correlation between immune subtypes and consensus molecular subtypes in colorectal cancer identifies novel tumour microenvironment profiles, with prognostic and therapeutic implications Eur J Cancer. (2019) 123:118-129.
Lázaro-Gorines R, Ruiz-de-la-Herrán J, Navarro R, Sanz L, Álvarez-Vallina L, Martínez-Del-Pozo A, Gavilanes JG, Lacadena J. A novel Carcinoembryonic Antigen (CEA)-Targeted Trimeric Immunotoxin shows significantly enhanced Antitumor Activity in Human Colorectal Cancer Xenografts. Sci Rep. (2019) 9:11680.
Mikkelsen K, Harwood SL, Compte M, Merino N, Mølgaard K, Lykkemark S, Alvarez-Mendez A, Blanco FJ, Álvarez-Vallina L. Carcinoembryonic Antigen (CEA)-Specific 4-1BB-Costimulation Induced by CEA-Targeted 4-1BB-Agonistic Trimerbodies. Front Immunol. (2019) 10:1791.
Rios X, Compte M, Gómez-Vallejo V, Cossío U, Baz Z, Morcillo MÁ, Ramos-Cabrer P, Alvarez-Vallina L, Llop J. Immuno-PET Imaging and Pharmacokinetics of an Anti-CEA scFv-based Trimerbody and Its Monomeric Counterpart in Human Gastric Carcinoma-Bearing Mice. Mol Pharm. (2019) 16:1025-1035.