HMarBCN -CNIO Cancer Immunotherapy Clinical Research Unit

Luis Álvarez-Vallina Head of Clinical Research Unit
T +34 000002950 (Ext 2950)
lalvarezv@ext.cnio.es

Post-Doctoral Fellows

Patricia Almendro
Patricia Hernández
Héctor Fernando Peláez
Daniel Salas
Laura Sanz
Antonio Tapia
Ivana Zagorac

Graduate Students

María Elena Barba
Jaime Franco
Marina Gómez
Gonzalo Raso
Lucía Rivas

Immune evasion is a critical step in cancer progression in which tumour cells modulate the host immune system to evade destruction. Our Unit focuses on understanding the molecular and cellular mechanisms of cancer immune evasion to develop more effective and safer cancer immunotherapies.

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

Reinvigorating endogenous tumour-specific T cell responses through the design of multi-specific antibodies against a combination of immunomodulatory targets, and the development of innovative RNA-delivery strategies. Preclinical and early clinical data show that this is a promising approach to enhance the clinical benefit of conventional checkpoint blockers.
Generating tumour reactive “artificial” T cell effectors by redirecting T cell activity towards cancer cells, targeting tumour-associated antigens (TAAs) with bispecific T cell-engaging (TCE) antibodies and/or membrane-anchored chimeric receptors (chimeric antigen receptors and/or chimeric costimulatory receptors).
Developing multi-targeted approaches for the simultaneous detection of extracellular and intracellular tumour antigens.
The Provision of personalised cancer treatments by bringing new immuno-oncology drugs and adoptive cell therapies to the clinic.

Recent publications

Zagorac I, Ramírez-Fernández Á, Tapia-Galisteo A, Rubio-Pérez L, Gómez-Rosel M, Grau M, Rodríguez-Peralto JL, Álvarez-Vallina L, Blanco B. (2026). mRNA-engineered T lymphocytes secreting bispecific T cell engagers with therapeutic potential in solid tumors. Front Inmmunol (in press). CNIO Publication.
Falgàs A, Lázaro-Gorines R, Zanetti SR, Rubio-Pérez L, Martinez-Moreno A, Vinyoles M, Guerrero-Murillo M, Fernandez-Fuentes N, Roca-Ho H, Tirado N, Panisello C, Velasco-Hernandez T, Mayado A, Pérez-Pons A, Genesca E, Ribera JM, Ribera J, Camos M, Ramírez-Orellana M, Anguita E, Ballerini P, Fuster JL, Juan M, González-Navarro EAA, Locatelli F, Stam RWW, Querol S, Velasco P, Ortiz-Maldonado V, Martínez-Cibrian N, Delgado J, Orfao A, Alvarez-Vallina L, Bueno C, Menendez P (2025). A TIM-3-Fc decoy secreted by engineered T cells improves CD19 CAR-T cell therapy in B-cell acute lymphoblastic leukemia.. Blood 145, 2599-2613. CNIO Publication.
Battistini E, Lapuhs P, Jiménez A, Garrido-Areal S, Rivas-Gómez L, Zagorac I, Álvarez-Vallina L, Alonso MJ, Sanjurjo L. (2025). Bispecific antibodies and nanotechnology: a strategic alliance in cancer immunotherapy. Mol Can 24, 292. Publication in other institutions.
Arroyo-Ródenas J, Falgas A, Díez-Alonso L, Martinez-Moreno A, Roca-Ho H, Gil-Etayo FJ, Pérez-Pons A, Aguilar-Sopeña Ó, Velasco-Sidro M, Gómez-Rosel M, Jiménez-Matías B, Muñoz-Sánchez G, Pacheco Y, Bravo-Martín C, Ramírez-Fernández Á, Jiménez-Reinoso A, González-Navarro EA, Juan M, Orfao A, Blanco B, Roda-Navarro P, Bueno C, Menéndez P, Álvarez-Vallina L. (2025). CD22 CAR-T cells secreting CD19 T-cell engagers for improved control of B-cell acute lymphoblastic leukemia progression. J Immunother Cancer 13, e009048. CNIO Publication.
Velasco-Sidro M, Arroyo-Ródenas J, Díez-Alonso L, Ramírez-Fernández Á, Álvarez-Vallina L. (2025). Dual-targeted STAb-T cells secreting BCMA and CD19 T cell engagers for improved control of haematological cancers. Oncoimmunology 14, 2444701. CNIO Publication.
Hangiu O, Navarro R, Frago S, Rubio-Pérez L, Tapia-Galisteo A, Díez-Alonso L, Gómez-Rosel M, Silva-Pilipich N, Vanrell L, Smerdou C, Howard KA, Sanz L, Álvarez-Vallina L, Compte M. (2025). Effective cancer immunotherapy combining mRNA-encoded bispecific antibodies that induce polyclonal T cell engagement and PD-L1-dependent 4-1BB costimulation. Front Inmmunol 15, 1494206. CNIO Publication.
Pilati D, Agyei EK, Elkhashab M, Fuchs E, Nielsen IH, Bjerg TW, Anthi AK, Jiménez-Reinoso A, Iversen MB, Pohl L, Narita R, Frago S, Jakobsen MR, Andersen JT, Degn SE, Paludan SR, Alvarez-Vallina L, Howard KA. (2025). Exploiting FcRn engagement of an albumin-CpG oligonucleotide covalent conjugate for potent TLR9 immune induction. J Biol Chem 301, 108508. CNIO Publication.
Salas-Lloret D, González-Prieto R. (2025). SUMO-Activated Target Traps (SATTs) for the Identification of Specific SUMOylated Proteins for an E3 Ligase of Interest. Methods Mol Biol 2957, 127-140. CNIO Publication.
Díez-Alonso L, Falgas A, Arroyo-Ródenas J, Romencín PA, Martínez A, Gómez-Rosel M, Blanco B, Jiménez-Reinoso A, Mayado A, Pérez-Pons A, Aguilar-Sopeña Ó, Ramírez-Fernández Á, Segura-Tudela A, Perez-Amill L, Tapia-Galisteo A, Domínguez-Alonso C, Rubio-Pérez L, Jara M, Solé F, Hangiu O, Almagro L, Albitre Á, Penela P, Sanz L, Anguita E, Valeri A, García-Ortiz A, Río P, Juan M, Martínez-López J, Roda-Navarro P, Martín-Antonio B, Orfao A, Menéndez P, Bueno C, Álvarez-Vallina L. (2024). Engineered T cells secreting anti-BCMA T cell engagers control multiple myeloma and promote immune memory in vivo. Sci Transl Med 16, adg7962. CNIO Publication. Open Access
Jiménez-Reinoso A, Molero-Abraham M, Cirauqui C, Blanco B, Garrido-Martin EM, Nehme-Álvarez D, Domínguez-Alonso C, Ramírez-Fernández Á, Díez-Alonso L, Nuñez-Buiza Á, González-Murillo Á, Tobes R, Pareja E, Ramírez-Orellana M, Rodriguez-Peralto JL, Ferrer I, Zugazagoitia J, Paz-Ares L, Álvarez-Vallina L. (2024). CD4+ tumor-infiltrating lymphocytes secreting T cell-engagers induce regression of autologous patient-derived non-small cell lung cancer xenografts.. Oncoimmunology 13, 2392897. CNIO Publication.
Tapia-Galisteo A, Sánchez-Rodríguez I, Narbona J, Iglesias-Hernández P, Aragón-García S, Jiménez-Reinoso A, Compte M, Khan S, Tsuda T, Chames P, Lacadena J, Álvarez-Vallina L, Sanz L. (2024). Combination of T cell-redirecting strategies with a bispecific antibody blocking TGF-β and PD-L1 enhances antitumor responses. Oncoimmunology 13, 2338558. CNIO Publication.
Navarro R, Frago S, Hangiu O, Erce-Llamazares A, Lázaro-Gorines R, Morcillo MA, Rodriguez-Peralto JL, Sanz L, Compte M, Alvarez-Vallina L. (2024). Pharmacokinetics and safety of LEAD-452, an EGFR-specific 4-1BB-agonistic trimerbody in non-human primates. Toxicol Appl Pharm 487, 116961. CNIO Publication.
Rubio-Pérez L, Frago S, Compte M, Navarro R, Harwood SL, Lázaro-Gorines R, Gómez-Rosel M, Hangiu O, Silva-Pilipich N, Vanrell L, Smerdou C, Álvarez-Vallina L (2024). Characterization of a Trispecific PD-L1 Blocking Antibody That Exhibits EGFR-Conditional 4-1BB Agonist Activity. Antibodies 13, 34. CNIO Publication.
Tapia-Galisteo A, Compte M, Álvarez-Vallina L, Sanz L. (2023). When three is not a crowd: trispecific antibodies for enhanced cancer immunotherapy.. Theranostics 13, 1028-1041. CNIO Publication.
Tapia-Galisteo A, Álvarez-Vallina L, Sanz L (2023). Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies. J Hematol Oncol 16, 83. CNIO Publication.
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 (2023). A PD-L1/EGFR bispecific antibody combines immune checkpoint blockade and direct anti-cancer action for an enhanced anti-tumor response.. Oncoimmunology 12, 2205336. CNIO Publication.
Lázaro-Gorines R, Pérez P, Heras-Murillo I, Adán-Barrientos I, Albericio G, Astorgano D, Flores S, Luczkowiak J, Labiod N, Harwood SL, Segura-Tudela A, Rubio-Pérez L, Nugraha Y, Shang X, Li Y, Alfonso C, Adipietro KA, Abeyawardhane DL, Navarro R, Compte M, Yu W, MacKerell AD Jr, Sanz L, Weber DJ, Blanco FJ, Esteban M, Pozharski E, Godoy-Ruiz R, Muñoz IG, Delgado R, Sancho D, García-Arriaza J, Álvarez-Vallina L. (2023). Dendritic Cell-Mediated Cross-Priming by a Bispecific Neutralizing Antibody Boosts Cytotoxic T Cell Responses and Protects Mice against SARS-CoV-2.. Adv Sci 10, e2304818. CNIO Publication.
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 (2022). Overcoming CAR-mediated CD19 downmodulation and leukemia relapse with T lymphocytes secreting anti-CD19 T cell engagers.. Cancer Immunol Res 10, 498-511. Publication in other institutions.
Jiménez-Reinoso A, Tirado N, Martinez-Moreno A, Diaz VM, García-Peydró M, Hangiu O, Diez-Alonso L, Albitre A, Penela P, Toribio ML, Menendez P, Alvarez-Vallina L, Sanchez Martinez D. (2022). Efficient treatment of cortical T cell acute lymphoblastic leukemia with T lymphocytes secreting anti-CD1a T cell engagers.. J Immunother Cancer 10, e005333. CNIO Publication. Open Access
Ramírez-Fernández A, Aguilar-Sopeña O, Díez-Alonso L, Segura-Tudela A, Domínguez-Alonso C, Álvarez-Vallina L, Blanco B (2022). Synapse topology and downmodulation events are determinant for the functional outcome of anti-CD19 T cell-redirecting strategies.. Oncoimmunology 11, 2054106. Publication in other institutions.
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 (2022). Trispecific T-cell engagers for dual tumor-targeting of colorectal cancer. Oncoimmunology 11, 2034355. Publication in other institutions.
Rousso-Noori L, Mastandrea I, Talmor S, Waks T, Globerson Levin A, Haugas M, Teesalu T, Alvarez-Vallina L, Eshhar Z, Friedmann-Morvinski D (2021). P32-specific CAR T cells with dual antitumor and antiangiogenic therapeutic potential in gliomas.. Nat Commun 12, 3615. Publication in other institutions. Open Access
Blanco B, Domínguez-Alonso C, Alvarez-Vallina L. (2021). Bispecific Immunomodulatory Antibodies for Cancer Immunotherapy.. Clin Cancer Res 27, 5457-5464. Publication in other institutions.
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. (2021). An Fc-free EGFR-specific 4-1BB-agonistic Trimerbody Displays Broad Antitumor Activity in Humanized Murine Cancer Models without Toxicity. Clin Cancer Res 27, 3167-3177. CNIO Publication.
Jiménez-Reinoso A, Nehme-Álvarez D, Domínguez-Alonso C, Álvarez-Vallina L. (2021). Synthetic TILs: Engineered Tumor-Infiltrating Lymphocytes With Improved Therapeutic Potential.. Front Oncol 10, 593848. Publication in other institutions.
Mandrup OA, Ong SC, Lykkemark S, Dinesen A, Rudnik-Jansen I, Dagnæs-Hansen NF, Andersen JT, Alvarez-Vallina L, Howard KA. (2021). Programmable half-life and anti-tumour effects of bispecific T-cell engager-albumin fusions with tuned FcRn affinity. Commun Biol 4, 310. Publication in other institutions.