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.
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.
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