H12O-CNIO Cancer Immunotherapy Clinical Research Unit

Luis Álvarez-Vallina Head of Clinical Research Unit
T +34 (+34) 917 328 000 (Ext 2950)
lalvarezv@ext.cnio.es

Research Scientists

Belén Blanco
Anais Jiménez

Post-Doctoral Fellows

Rodrigo Lázaro
Daniel Salas
Antonio Tapia
Ivana Zagorac

Graduate Students

Francisco Javier Arroyo
María Elena Barba
Eva García
Marina Gómez
Susana Luengo
Lucía Rivas
Laura Rubio
Alejandro Segura
Miriam Velasco

Technicians

María de la Yedra Pacheco

Visiting Scientist

Manal Mohamed Elsayed Ahmed
Philipp Lapuhs

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:

Reactivation of tumour-specific endogenous T cell repertoires through the design of multi-specific antibodies against a combination of immunomodulatory targets. Preclinical and early clinical data show that this is a promising approach to enhance the clinical benefit of conventional checkpoint blockers.
Generation of 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).
Development of multi-target approaches that simultaneously recognise extracellular and intracellular tumour antigens.
Rational design of mRNA-based therapeutics.
Provision of personalised cancer treatments by bringing new immuno-oncology drugs and adoptive cell therapies to the clinic.

Publications

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, 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.
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.
Blanco B, Compte M, Lykkemark S, Sanz L, Alvarez-Vallina L. (2019). T Cell-Redirecting Strategies to ‘STAb’ Tumors: Beyond CARs and Bispecific Antibodies.. Trends Immunol 40, 243-257. Publication in other institutions.
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 (2019). 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 123, 118-129. CNIO Publication.