Article
Immunology
Ursa Lampreht Tratar, Nina Milevoj, Maja Cemazar, Katarina Znidar, Katja Ursic Valentinuzzi, Andreja Brozic, Katerina Tomsic, Gregor Sersa, Natasa Tozon
Summary: This study compared the intratumoral (i.t.) and peritumoral (peri.t.) routes of interleukin-12 (IL-12) gene electrotransfer (GET) in combination with electrochemotherapy (ECT). The results showed that intratumoral administration had better treatment outcomes, with significantly improved local tumor control, longer disease-free interval, and progression-free survival compared to the other routes.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Ayse Ercan, Mustafa Celebier, Selin Oncul, Gamze Varan, Engin Kocak, Juan M. Benito, Erem Bilensoy
Summary: This study highlights the potential of novel nanoparticles for treating hepatocellular carcinoma by inhibiting cell proliferation, inducing apoptosis, and reducing multidrug resistance. Blank nanoparticles were able to restore chemosensitivity in HCC cells.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Oncology
Yuanming Xu, Lucia Campos Carrascosa, Yik Andy Yeung, Matthew Ling-Hon Chu, Wenjing Yang, Ivana Djuretic, Danielle C. Pappas, John Zeytounian, Zhouhong Ge, Valeska de Ruiter, Gabriel R. Starbeck-Miller, James Patterson, Diamanda Rigas, Shih-Hsun Chen, Eugenia Kraynov, Patrick P. Boor, Lisanne Noordam, Michael Doukas, Dave Tsao, Jan N. Ijzermans, Jie Guo, Dirk J. Grunhagen, Joris Erdmann, Joanne Verheij, Martin E. van Royen, Pascal G. Doornebosch, Renny Feldman, Terrence Park, Salah Mahmoudi, Magdalena Dorywalska, Irene Ni, Sherman M. Chin, Tina Mistry, Lidia Mosyak, Laura Lin, Keith A. Ching, Kevin C. Lindquist, Changhua Ji, Luz Marina Londono, Bing Kuang, Robert Rickert, Jaap Kwekkeboom, Dave Sprengers, Tzu-Hsuan Huang, Javier Chaparro-Riggers
Summary: The study engineered a novel immunocytokine, anti-PD1-IL15m, that targets PD1+ tumor-infiltrating lymphocytes to enhance the efficacy and safety of IL15 in cancer immunotherapy.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Cell Biology
Dimitris Stellas, Sevasti Karaliota, Vasiliki Stravokefalou, Matthew Angel, Bethany A. Nagy, Katherine C. Goldfarbmuren, Cristina Bergamaschi, Barbara K. Felber, George N. Pavlakis
Summary: In a triple-negative breast cancer (TNBC) orthotopic mouse model, locoregional monotherapy with heterodimeric interleukin (IL)-15 (hetIL-15) led to tumor eradication in 40% of treated mice, reduction of metastasis, and development of immunological memory. hetIL-15 reshaped the tumor microenvironment by promoting the accumulation of cytotoxic lymphocytes, conventional type 1 dendritic cells (cDC1s), and a dendritic cell (DC) population expressing both CD103 and CD11b markers. The hetIL-15-induced CD103intCD11b+ DC population has characteristics resembling both cDC1s and cDC2s, and is associated with tumor regression.
Article
Cell Biology
Hyesol Lim, Minsoo Koh, Hao Jin, Mijeong Bae, Seung-Yeon Lee, Kyoung Mee Kim, Joohee Jung, Hyun Jeong Kim, So Yeon Park, Hoe Suk Kim, Woo Kyung Moon, Sejin Hwang, Nam Hoon Cho, Aree Moon
Summary: CAFs can induce an invasive phenotype in non-neoplastic breast epithelial cells, with IL-8 and S100A8 playing a crucial role in this process. Targeting IL-8 and S100A8 may be an effective strategy against breast cancer progression.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Kyoung-Ju Kim, Dahye Moon, So Jung Kong, Yu Seong Lee, Youngeun Yoo, Soyoung Kim, Chan Kim, Hong Jae Chon, Joo-Hang Kim, Kyung-Ju Choi
Summary: This study demonstrated the synergistic effect of IL-12 and GM-CSF from an engineered oncolytic HSV, enhancing the immune response and improving the antitumor effects, particularly in inhibiting tumor growth and prolonging survival in a murine melanoma model. Increased activation of CD4(+) and CD8(+) T cells, along with enhanced IFN-gamma production and cytotoxic immune response, were observed in mice treated with increment 6/GM/IL12 compared to those treated with increment 6/GM or increment 6/IL12 expressing each individual cytokine.
Article
Engineering, Biomedical
Patrick Reichenbach, Greta Maria Paola Giordano Attianese, Khaoula Ouchen, Elisabetta Cribioli, Melanie Triboulet, Sarah Ash, Margaux Saillard, Romain Vuillefroy de Silly, George Coukos, Melita Irving
Summary: This study reports the design and production of a lentiviral vector that incorporates two functionally independent promoters, allowing for the expression of a tumour-directed receptor and inducible gene in T cells. The vector enables the delivery of various genes to human T cells, improving the safety and efficacy of T-cell therapies.
NATURE BIOMEDICAL ENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Huaijun Wang, Jose G. Vilches-Moure, Thierry Bettinger, Samir Cherkaoui, Amelie Lutz, Ramasamy Paulmurugan
Summary: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder that requires non-invasive quantitative imaging tools for monitoring disease activity and treatment response. This study evaluated the use of dual P- and E-selectin-targeted microbubbles for ultrasound molecular imaging in a chronic IBD mouse model, providing insights into long-term anti-inflammatory effects and potential treatment assessment.
Article
Microbiology
Haruyo Nakajima-Adachi, Masato Tamai, Haruka Nakanishi, Satoshi Hachimura
Summary: This study found that extracts from Gluconacetobacter hansenii GK-1, a type of acetic acid bacteria, can inhibit the production of interleukin-4 (IL-4) by immune cells, improving allergic symptoms. These extracts also promote the differentiation of regulatory T cells.
BIOSCIENCE OF MICROBIOTA FOOD AND HEALTH
(2022)
Article
Cell Biology
Leyre Lopez-Muneta, Javier Linares, Oscar Casis, Laura Martinez-Ibanez, Arantxa Gonzalez Miqueo, Jaione Bezunartea, Ana Maria Sanchez de la Nava, Monica Gallego, Maria Eugenia Fernandez-Santos, Juan Roberto Rodriguez-Madoz, Xabier L. Aranguren, Francisco Fernandez-Aviles, Jose Carlos Segovia, Felipe Prosper, Xonia Carvajal-Vergara
Summary: This study successfully generated functional human NKX2.5(GFP) reporter cardiac fibroblasts, which provide unlimited cellular models and potential progress for cardiac reprogramming research.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Flor Navarro, Noelia Casares, Celia Martin-Otal, Aritz Lasarte-Cia, Marta Gorraiz, Patricia Sarrion, Diana Llopiz, David Reparaz, Nerea Varo, Juan Roberto Rodriguez-Madoz, Felipe Prosper, Sandra Hervas-Stubbs, Teresa Lozano, Juan Jose Lasarte
Summary: The acidification of the tumor microenvironment inhibits the activity of antitumor T cells. Inhibiting the acid loader Ae2 enhances T cell function, while silencing Ae2 or overexpressing Hvcn1 improves the antitumor activity of T cells.
Article
Medicine, Research & Experimental
Rebeca Martinez-Turrillas, Angel Martin-Mallo, Saray Rodriguez-Diaz, Natalia Zapata-Linares, Paula Rodriguez-Marquez, Patxi San Martin-Uriz, Amaia Vilas-Zornoza, Maria E. Calleja-Cervantes, Eduardo Salido, Felipe Prosper, Juan R. Rodriguez-Madoz
Summary: This study demonstrates the efficacy of liver-specific inhibition of lactate dehydrogenase (LDH) using CRISPR-Cas9 systems for treating primary hyperoxalurias (PHs). The inhibition led to reduced levels of LDH in the liver, resulting in decreased urine oxalate levels and kidney damage without any signs of toxicity. The findings suggest that in vivo genome editing with CRISPR-Cas9 systems could be a valuable tool for improving therapeutic approaches for PH.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Review
Oncology
Sonia Guedan, Maik Luu, Delphine Ammar, Paula Barbao, Chiara Bonini, Philippe Bousso, Christian J. Buchholz, Monica Casucci, Biagio De Angelis, Emmanuel Donnadieu, David Espie, Beatrice Greco, Richard Groen, Johannes B. Huppa, Chahrazade Kantari-Mimoun, Bruno Laugel, Mary Mantock, Janet L. Markman, Emma Morris, Concetta Quintarelli, Michael Rade, Kristin Reiche, Alba Rodriguez-Garcia, Juan Roberto Rodriguez-Madoz, Eliana Ruggiero, Maria Themeli, Michael Hudecek, Ibtissam Marchiq
Summary: Immunotherapy with gene engineered CAR and TCR transgenic T-cells is a groundbreaking treatment in cancer medicine, and has the potential to be used in common solid tumors. However, in order to improve and accelerate the selection of lead T-cell products for clinical translation, it is necessary to assess preclinical models and develop new models with higher predictive value.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biology
Jianhao Peng, Guillermo Serrano, Ian M. Traniello, Maria E. Calleja-Cervantes, Ullas V. Chembazhi, Sushant Bangru, Teresa Ezponda, Juan Roberto Rodriguez-Madoz, Auinash Kalsotra, Felipe Prosper, Idoia Ochoa, Mikel Hernaez
Summary: Single-cell RNA-Sequencing is a powerful tool for studying complex regulatory interactions between diverse cell phenotypes. However, current methods are limited in their ability to uncover complex regulatory relationships across related cell types. The presented framework, SimiC, overcomes this limitation by inferring distinct regulatory dynamics per phenotype. SimiC has shown to uncover key regulatory patterns missed by previous methods, with implications for systems biology.
COMMUNICATIONS BIOLOGY
(2022)
Article
Agriculture, Dairy & Animal Science
Marta Moya-Jodar, Giulia Coppiello, Juan Roberto Rodriguez-Madoz, Gloria Abizanda, Paula Barlabe, Amaia Vilas-Zornoza, Asier Ullate-Agote, Chiara Luongo, Ernesto Rodriguez-Tobon, Sergio Navarro-Serna, Evelyne Paris-Oller, Maria Oficialdegui, Xonia Carvajal-Vergara, Laura Ordovas, Felipe Prosper, Francisco Alberto Garcia-Vazquez, Xabier L. Aranguren
Summary: The generation of organs using pluripotent stem cells combined with genetically engineered pig embryos through blastocyst complementation could provide a solution to the worldwide shortage of transplantable organs. In this study, a protocol to create vascular-disabled pig embryos using the CRISPR/Cas9 system was optimized, which could contribute to the generation of rejection-free humanized organs in pigs.
Article
Biotechnology & Applied Microbiology
Enrique Conde, Noelia Casares, Uxua Mancheno, Edurne Elizalde, Enric Vercher, Roberto Capozzi, Eva Santamaria, Juan R. Rodriguez-Madoz, Felipe Prosper, Juan J. Lasarte, Teresa Lozano, Sandra Hervas-Stubbs
Summary: Regulatory T cells with FOXP3 overexpression in the tumor microenvironment (TME) have a metabolic advantage, leading to improved antitumor efficacy of CD8 T cells. These FOXP3overexpressing CD8 T cells exhibit tissue-resident memory-like and effector T cell features, with enriched metabolic pathways such as glycolysis, fatty acid metabolism, and oxidative phosphorylation. They compensate for ATP production loss through aerobic glycolysis and engage in fatty acid oxidation for energy demands. This ability to couple glycolysis and oxidative phosphorylation allows them to sustain proliferation under glucose restriction, enhancing their effectiveness in adoptive T cell therapy (ACT).
Article
Medicine, Research & Experimental
Noelia Silva-Pilipich, Aritz Lasarte-Cia, Teresa Lozano, Celia Martin-Otal, Juan Jose Lasarte, Cristian Smerdou
Summary: Local delivery of alphavirus vectors based on self-amplifying RNA through in vivo electroporation shows promising results in antitumor therapy, especially when combined with PD-1 blockade, suggesting it as an attractive strategy for cancer immunotherapy.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Multidisciplinary Sciences
Paula Rodriguez-Marquez, Maria E. Calleja-Cervantes, Guillermo Serrano, Aina Oliver-Caldes, Maria L. Palacios-Berraquero, Angel Martin-Mallo, Cristina Calvino, Marta Espanol-Rego, Candela Ceballos, Teresa Lozano, Patxi San Martin-Uriz, Amaia Vilas-Zornoza, Saray Rodriguez-Diaz, Rebeca Martinez-Turrillas, Patricia Jauregui, Diego Alignani, Maria C. Viguria, Margarita Redondo, Mariona Pascal, Beatriz Martin-Antonio, Manel Juan, Alvaro Urbano-Ispizua, Paula Rodriguez-Otero, Ana Alfonso-Pierola, Bruno Paiva, Juan J. Lasarte, Susana Inoges, Ascension Lopez-Diaz de Cerio, Jesus San-Miguel, Carlos Fernandez de Larrea, Mikel Hernaez, Juan R. Rodriguez-Madoz, Felipe Prosper
Summary: This study investigates the impact of CAR density on the functionality and clinical response of BCMA CAR T cells. It found that CAR T cells with high expression of the CAR construct have increased tonic signaling, up-regulation of exhaustion markers, and increased cytotoxicity in vitro but decreased bone marrow infiltration in vivo. Patients treated with CAR T cell products enriched in CAR(High) T cells show significantly worse clinical response in several hematological malignancies.
Article
Oncology
Celia Martin-Otal, Aritz Lasarte-Cia, Diego Serrano, Noelia Casares, Enrique Conde, Flor Navarro, Ines Sanchez-Moreno, Marta Gorraiz, Patricia Sarrion, Alfonso Calvo, Carlos E. De Andrea, Jose Echeveste, Amaia Vilas, Juan Roberto Rodriguez-Madoz, Jesus San Miguel, Felipe Prosper, Sandra Hervas-Stubbs, Juan Jose Lasarte, Teresa Lozano
Summary: This study demonstrates the feasibility and efficacy of targeting the tumor-specific fibronectin splice variant EDA with CAR-T cells, providing a potential therapeutic option for different types of cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Meeting Abstract
Hematology
Lorea Jordana-Urriza, Guillermo Serrano, Maria Erendira Calleja-Cervantes, Patxi San Martin-Uriz, Amaia Vilas-Zornoza, Asier Ullate-Agote, Aintzane Zabaleta, Diego Alignani, Teresa Lozano, Valentin Cabanas, Almudena Navarro-Bailon, Aina Oliver-Caldes, Marta Espanol-Rego, Mariona Pascal, Manel Juan, Alvaro Urbano-Ispizua, Juan Luis Reguera, Jose Maria Moraleda, Maria-Victoria Mateos, Fermin Sanchez-Guijo, Ana Alfonso Pierola, Jose J. Rifon Roca, Paula Rodriguez-Otero, Carlos Fernandez de Larrea, Bruno Paiva, Susana Inoges, Ascension Lopez-Diaz De Cerio, Juan Jose Lasarte, Jesus San-Miguel, Juan Roberto Rodriguez-Madoz, Mikel Hernaez, Felipe Prosper
Meeting Abstract
Hematology
Angel Martin-Mallo, Maria Erendira Calleja-Cervantes, Patxi San Martin-Uriz, Amaia Vilas-Zornoza, Aintzane Zabaleta, Diego Alignani, Paula Rodriguez-Marquez, Saray Rodriguez-Diaz, Rebeca Martinez-Turrillas, Patricia Jauregui, Cristina Calvino, Maria Luisa Palacios-Berraquero, Candela Ceballos, Jorge Illarramendi Esteban, Diana Gisell Gabaldon Limas, Maria Cruz Viguria, Ana Margarita Redondo, Manel Juan, Alvaro Urbano-Ispizua, Carlos Fernandez de Larrea, Paula Rodriguez-Otero, Jose J. Rifon Roca, Ana Alfonso Pierola, Teresa Lozano, Juan Jose Lasarte, Bruno Paiva, Susana Inoges, Ascension Lopez-Diaz De Cerio, Jesus San-Miguel, Juan Roberto Rodriguez-Madoz, Felipe Prosper
Article
Cell & Tissue Engineering
Marta Moya-Jodar, Asier Ullate-Agote, Paula Barlabe, Juan Roberto Rodriguez-Madoz, Gloria Abizanda, Carolina Barreda, Xonia Carvajal-Vergara, Amaia Vilas-Zornoza, Juan Pablo Romero, Leire Garate, Xabier Agirre, Giulia Coppiello, Felipe Prosper, Xabier L. Aranguren
Summary: In this study, distinct cell populations coexisting with epiblast-like cells in 5iLAF naive human induced pluripotent stem cell (hiPSC) cultures were discovered and characterized. These cell populations closely resemble different cell types of the human embryo at early developmental stages. The presence of a totipotent eight-cell (8C)-stage-like cell population, as well as three populations analogous to trophectoderm cells at different maturation stages, and cells resembling primitive endoderm were detected. This provides an excellent opportunity to model the earliest events of human embryogenesis using 5iLAF naive hiPSC cultures.
Article
Immunology
Cristina Calvino, Candela Ceballos, Ana Alfonso, Patricia Jauregui, Maria E. Calleja-Cervantes, Patxi San Martin-Uriz, Paula Rodriguez-Marquez, Angel Martin-Mallo, Elena Iglesias, Gloria Abizanda, Saray Rodriguez-Diaz, Rebeca Martinez-Turrillas, Jorge Illarramendi, Maria C. Viguria, Margarita Redondo, Jose Rifon, Sara Villar, Juan J. Lasarte, Susana Inoges, Ascension Lopez-Diaz de Cerio, Mikel Hernaez, Felipe Prosper, Juan R. Rodriguez-Madoz
Summary: Despite the potential of CAR-T therapies, their efficacy in patients with relapse and refractory Acute Myeloid Leukemia (AML) has been limited. In this study, we aimed to develop and manufacture CAR-T cells that overcome the limitations observed in AML patients. Our findings show that CAR-T cells from AML patients have an exhausted effector phenotype, compared to healthy donors, which compromises their antitumoral efficacy. By combining CRISPR technologies with transposon-based delivery strategies, we successfully generated modified CAR-T cells that demonstrate similar phenotypic and functional profiles to non-modified CAR-T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Meeting Abstract
Biotechnology & Applied Microbiology
C. Martin-Otal, A. Lasarte-Cia, D. Serrano, N. Casares, F. Navarro, P. Sarrion, M. Gorraiz, C. De-Andrea, J. Echeveste, J. R. Rodriguez-Madoz, J. San Miguel, F. Prosper, S. Hervas-Stubbs, J. J. Lasarte, T. Lozano
HUMAN GENE THERAPY
(2022)