Immune evasion is a fundamental mechanism of tumor progression. Cancer cells use different strategies to evade host immune surveillance and resist immune-mediated elimination. These strategies include altering antigen presentation, secreting immunosuppressive factors, recruiting regulatory immune cell subsets, and expressing immune checkpoint ligands. A deeper understanding of these processes is critical for developing next-generation immunotherapies.
The Cancer Immunotherapy Clinical Research Unit is dedicated to elucidating the molecular and cellular mechanisms that drive immune evasion in cancer. Our ultimate goal is to design more precise, effective, and safe cancer immunotherapy strategies. We accomplish this by integrating mechanistic studies with translational and clinical development, which helps us overcome the limitations of current immuno-oncology approaches.
Our scientific focus encompasses several interconnected areas:
Reactivation of tumor-specific endogenous T cell responses through the development of multispecific antibodies targeting immunoregulatory receptors; This strategy aims to reverse T cell dysfunction and augment anti-tumor immunity. Preclinical and early-phase clinical data support its potential to synergize with and improve the efficacy of established immune checkpoint inhibitors.
Engineering of synthetic, tumor-reactive T cell effectors to redirect T cell specificity toward tumor-associated antigens (TAAs) using bispecific T cell-engaging (TCE) antibodies and genetically encoded synthetic receptors. These include chimeric antigen receptors (CARs) and chimeric costimulatory receptors (CCRs), which enable antigen-specific activation and costimulation within the tumor microenvironment.
Developing multi-target immunotherapeutic platforms that simultaneously recognize extracellular and intracellular tumor antigens. These strategies aim to mitigate tumor antigen escape and enhance recognition of tumor heterogeneity by expanding the antigenic repertoire.
Design and optimization of mRNA-based therapeutic modalities, including mRNA-encoded antibodies and immune-modulating factors. These approaches allow for the transient and controlled expression of therapeutic proteins, making them well-suited for personalized and combinatorial strategies.
We translate novel immunotherapies into personalized treatment regimens, including the clinical development of investigational immuno-oncology agents and adoptive cell therapies. Through biomarker-driven patient selection and precision immunotherapy frameworks, we aim to tailor interventions to individual tumor-immune profiles.
Publicaciones
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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 (in press). Publicación CNIO.
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. Publicación CNIO.
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. Publicación CNIO. Open Access
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. Publicación CNIO.
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.
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.
Open Access