Unidad de Investigación Clínica en Inmunoterapia del Cáncer H12O-CNIO

Luis Álvarez-Vallina Jefe de Unidad de Investigación Clínica
T +34 (+34) 917 328 000 (Ext )
lalvarezv@extcnio.es

Investigadores

Belén Blanco
Anais Jiménez

Becarios Post-doctorales

Rodrigo Lázaro
Ángel Ramírez
Antonio Tapia
Ivana Zagorac

Becarios Pre-Doctorales

Francisco Javier Arroyo
Laura Díez
Carmen Domínguez
Marina Gómez
Laura Rubio
Alejandro Segura
Miriam Velasco

Técnicos de Laboratorio

María de la Yedra Pacheco

Immunotherapy has opened a new era in cancer treatment. 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: 1) reactivation (rescue) of pre-existing tumor-specific endogenous T cell repertoires(e.g., tumor-infiltrating lymphocytes), 2) development of T cell redirecting strategies to improve the clinical efficacy and safety profile of tumor-reactive artificial T cells, and 3) development of multi-targeting approaches recognizing tumor-associated antigens (TAA) and/or tumor-specific antigens (TSA) at both extra- and intracellular locations. Moreover, our group has a strong interest in the generation of multivalent and multispecific antibody formats and the use of engineered mRNA-based gene delivery systems. Finally, our Unit has a firm commitment to introduce new immuno-oncology drugs and adoptive cell therapies in the clinic, to provide high-quality personalized treatments.

Publicaciones

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. Publicación en otras instituciones.
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. Publicación CNIO.
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. Publicación en otras instituciones.
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. Publicación en otras instituciones.
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. Publicación en otras instituciones. Open Access
Blanco B, Domínguez-Alonso C, Alvarez-Vallina L. (2021). Bispecific Immunomodulatory Antibodies for Cancer Immunotherapy.. Clin Cancer Res 27, 5457-5464. Publicación en otras instituciones.
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. Publicación CNIO.
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. Publicación en otras instituciones.
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. Publicación en otras instituciones.
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. Publicación en otras instituciones.
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. Publicación CNIO.
Compte M, Harwood SL, Muñoz IG, Navarro R, Zonca M, Perez-Chacon G, Erce-Llamazares A, Merino N, Tapia-Galisteo A, Cuesta AM, Mikkelsen K, Caleiras E, Nuñez-Prado N, Aznar MA, Lykkemark S, Martínez-Torrecuadrada J, Melero I, Blanco FJ, Bernardino de la Serna J, Zapata JM, Sanz L, Alvarez-Vallina L (2018). A tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity. Nat Commun 9, 4809. Publicación CNIO. Open Access
Mølgaard K, Harwood SL, Compte M, Merino N, Bonet J, Alvarez-Cienfuegos A, Mikkelsen K, Nuñez-Prado N, Alvarez-Mendez A, Sanz L, Blanco FJ, Alvarez-Vallina L (2018). Bispecific light T-cell engagers for gene-based immunotherapy of epidermal growth factor receptor (EGFR)-positive malignancies. Cancer Immunol Immun 67, 1251-1260. Publicación en otras instituciones.