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Your search keyword '"A. Garcias López"' showing total 9 results
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9 results on '"A. Garcias López"'

1. Tumor-agnostic cancer therapy using antibodies targeting oncofetal chondroitin sulfate

Author

Elena Ethel Vidal-Calvo, Anne Martin-Salazar, Swati Choudhary, Robert Dagil, Sai Sundar Rajan Raghavan, Lara Duvnjak, Mie Anemone Nordmaj, Thomas Mandel Clausen, Ann Skafte, Jan Oberkofler, Kaituo Wang, Mette Ø Agerbæk, Caroline Løppke, Amalie Mundt Jørgensen, Daria Ropac, Joana Mujollari, Shona Willis, Agnès Garcias López, Rebecca Louise Miller, Richard Torbjörn Gustav Karlsson, Felix Goerdeler, Yen-Hsi Chen, Ana R. Colaço, Yong Wang, Thomas Lavstsen, Agnieszka Martowicz, Irina Nelepcu, Mona Marzban, Htoo Zarni Oo, Maj Sofie Ørum-Madsen, Yuzhuo Wang, Morten A. Nielsen, Henrik Clausen, Michael Wierer, Dominik Wolf, Ismail Gögenur, Thor G. Theander, Nader Al-Nakouzi, Tobias Gustavsson, Mads Daugaard, and Ali Salanti

Subjects
Science
Abstract

Abstract Molecular similarities between embryonic and malignant cells can be exploited to target tumors through specific signatures absent in healthy adult tissues. One such embryonic signature tumors express is oncofetal chondroitin sulfate (ofCS), which supports disease progression and dissemination in cancer. Here, we report the identification and characterization of phage display-derived antibody fragments recognizing two distinct ofCS epitopes. These antibody fragments show binding affinity to ofCS in the low nanomolar range across a broad selection of solid tumor types in vitro and in vivo with minimal binding to normal, inflamed, or benign tumor tissues. Anti-ofCS antibody drug conjugates and bispecific immune cell engagers based on these targeting moieties disrupt tumor progression in animal models of human and murine cancers. Thus, anti-ofCS antibody fragments hold promise for the development of broadly effective therapeutic and diagnostic applications targeting human malignancies.

Published
2024
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2. Tumor-agnostic cancer therapy using antibodies targeting oncofetal chondroitin sulfate.

Author

Vidal-Calvo, Elena Ethel, Martin-Salazar, Anne, Choudhary, Swati, Dagil, Robert, Raghavan, Sai Sundar Rajan, Duvnjak, Lara, Nordmaj, Mie Anemone, Clausen, Thomas Mandel, Skafte, Ann, Oberkofler, Jan, Wang, Kaituo, Agerbæk, Mette Ø, Løppke, Caroline, Jørgensen, Amalie Mundt, Ropac, Daria, Mujollari, Joana, Willis, Shona, Garcias López, Agnès, Miller, Rebecca Louise, and Karlsson, Richard Torbjörn Gustav

Subjects
CHONDROITIN sulfates, CANCER cells, FETAL tissues, BENIGN tumors, CANCER invasiveness, TARGETED drug delivery, NANOMEDICINE
Abstract

Molecular similarities between embryonic and malignant cells can be exploited to target tumors through specific signatures absent in healthy adult tissues. One such embryonic signature tumors express is oncofetal chondroitin sulfate (ofCS), which supports disease progression and dissemination in cancer. Here, we report the identification and characterization of phage display-derived antibody fragments recognizing two distinct ofCS epitopes. These antibody fragments show binding affinity to ofCS in the low nanomolar range across a broad selection of solid tumor types in vitro and in vivo with minimal binding to normal, inflamed, or benign tumor tissues. Anti-ofCS antibody drug conjugates and bispecific immune cell engagers based on these targeting moieties disrupt tumor progression in animal models of human and murine cancers. Thus, anti-ofCS antibody fragments hold promise for the development of broadly effective therapeutic and diagnostic applications targeting human malignancies. Cancer cells often acquire molecular patterns of fast-growing embryonic tissues to enable propagation and invasion, which distinguish tumour tissues from their healthy adult counterpart. Here authors develop antibody fragments which specifically target oncofetal chondroitin sulphate on the cancer cell surface and in the tumour stroma, with the antibodies achieving therapeutic effect in multiple mouse models in antibody drug conjugate and bispecific immune cell engager formats. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Bicistronic CAR T Cell Against CD229 and BCMA Effectively Controls Multiple Myeloma

Author

Rodríguez-Lobato, Luis Gerardo, primary, Cardus, Oriol, additional, Mañe-Pujol, Joan, additional, Battram, Anthony M, additional, Pérez-Amill, Lorena, additional, Calderón, Hugo, additional, Martin-Antonio, Beatriz, additional, Oliver-Caldes, Aina, additional, Garcias-López, Agnès, additional, Lozano, Ester, additional, Moreno, David F., additional, Ortiz-Maldonado, Valentín, additional, Salas, Maria Queralt, additional, de Daniel i Bisbe, Anna, additional, Tovar, Natalia, additional, Jiménez-Segura, Raquel, additional, Cibeira, M. Teresa, additional, Rosinol Dachs, Laura, additional, Bladé Creixenti, Joan, additional, Juan, Manel, additional, Urbano-Ispizua, Álvaro, additional, Engel, Pablo, additional, and Fernandez de Larrea, Carlos, additional

Published
2022
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4. αvβ8 integrin-expression by BATF3-dependent dendritic cells facilitates early IgA responses to Rotavirus

Author

Bernard Malissen, Joy Nakawesi, Julia Hütter, Sébastien This, Harry B. Greenberg, L. J. Gooday, A. Garcias López, V. Barateau, Katharina Lahl, K. Getachew Muleta, K. Fog Thomsen, Olivier Thaunat, M. Boucard-Jourdin, T. Defrance, Didier Poncet, Isabel Ulmert, H. Paidassi, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Lund University [Lund], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Technical University of Denmark - Division of Biopharma - Institut for Health Tech - Kongens, Berlin Institute of Health (BIH), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Stanford University School of Medicine [CA, USA], VA Palo Alto Health Care System, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), ANR-13-PDOC-0019,InteReg,Régulation de l'expression de l'intégrine alpha-v-beta-8 et son rôle dans le maintien de l'homéostasie immunitaire de l'intestin(2013), Biologie Moléculaire des Rotavirus (ROTA), Département Virologie (Dpt Viro), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Paul Scherrer Institute (PSI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Rotavirus, 0301 basic medicine, Integrins, HOMEOSTASIS, [SDV]Life Sciences [q-bio], Immunology, Integrin, Context (language use), Antibodies, Viral, medicine.disease_cause, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Rotavirus Infections, Virus, ACTIVATION, 03 medical and health sciences, 0302 clinical medicine, Antibody Specificity, INFECTION, TGF beta signaling pathway, medicine, Immunology and Allergy, Mesenteric lymph nodes, TGF-BETA-1, REGULATORY T-CELLS, ComputingMilieux_MISCELLANEOUS, TGF beta 1, biology, GROWTH-FACTOR-BETA, INDUCTION, TGF-BETA, Dendritic Cells, Immunoglobulin A, 3. Good health, Basic-Leucine Zipper Transcription Factors, 030104 developmental biology, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, B-CELLS, Host-Pathogen Interactions, Immunoglobulin A, Secretory, biology.protein, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Homeostasis, 030215 immunology
Abstract

International audience; Secretory intestinal IgA can protect from re-infection with rotavirus (RV), but very little is known about the mechanisms that induce IgA production during intestinal virus infections. Classical dendritic cells (cDCs) in the intestine can facilitate both T cell-dependent and -independent secretory IgA. Here, we show that BATF3-dependent cDC1, but not cDC2, are critical for the optimal induction of RV-specific IgA responses in the mesenteric lymph nodes. This depends on the selective expression of the TGF beta-activating integrin alpha v beta 8 by cDC1. In contrast, alpha v beta 8 on cDC1 is dispensible for steady state immune homeostasis. Given that cDC2 are crucial in driving IgA during steady state but are dispensable for RV-specific IgA responses, we propose that the capacity of DC subsets to induce intestinal IgA responses reflects the context, as opposed to an intrinsic property of individual DC subsets.

Published
2021

5. Bicistronic CAR T Cell Against CD229 and BCMA Effectively Controls Multiple Myeloma

Author

Luis Gerardo Rodríguez-Lobato, Oriol Cardus, Joan Mañe-Pujol, Anthony M Battram, Lorena Pérez-Amill, Hugo Calderón, Beatriz Martin-Antonio, Aina Oliver-Caldes, Agnès Garcias-López, Ester Lozano, David F. Moreno, Valentín Ortiz-Maldonado, Maria Queralt Salas, Anna de Daniel i Bisbe, Natalia Tovar, Raquel Jiménez-Segura, M. Teresa Cibeira, Laura Rosinol Dachs, Joan Bladé Creixenti, Manel Juan, Álvaro Urbano-Ispizua, Pablo Engel, and Carlos Fernandez de Larrea

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

6. AU Content in the MicroRNA Sequence Influences its Stability after Heat Treatment

Author

Agnès Garcias López, Susanna Cirera, Kerstin Skovgaard, Louise Brogaard, and Peter Mikail Helwag Heegaard

Subjects
0301 basic medicine, Saliva, Hot Temperature, Swine, RNase P, RNA Stability, 03 medical and health sciences, chemistry.chemical_compound, Ribonucleases, 0302 clinical medicine, Gene expression, microRNA, Leukocytes, Animals, Orthopedics and Sports Medicine, Uracil, Lung, chemistry.chemical_classification, Base Composition, Base Sequence, Adenine, RNA, General Medicine, MicroRNAs, 030104 developmental biology, Enzyme, chemistry, Biochemistry, 030220 oncology & carcinogenesis, Emergency Medicine, Digestion
Abstract

Background: MicroRNAs (miRNAs) are short non-coding RNA molecules which regulate gene expression post-transcriptionally and are involved in a multitude of cellular processes. MiRNAs are known to be very stable compared to messenger RNAs (mRNAs), making them excellent candidates as biomarkers for disease. Recently, studies have suggested that miRNA stability in formalin fixed samples might depend on their nucleotide composition. Objective: To explore the stability of a panel of miRNAs isolated from porcine blood and lung tissue after heat and enzyme treatment. Method: Porcine RNA isolated from lung tissue and blood leukocytes was used for this study. RNA samples were exposed to heat treatment and RNAse A digestion. The levels of selected miRNAs were measured by means of qPCR before and after heat and enzyme treatment. Results: Fourteen miRNAs were successfully analysed, and they were found to degrade differently after exposure to heat or RNAse A. MiRNAs with Conclusion: This is the first study showing that different miRNAs isolated from lung tissue display unequal stability after heat treatment, probably based on their nucleotide composition, highlighting the importance of considering the miRNA sequence when investigating their value as biomarkers.

Published
2019

7. Migration of murine intestinal dendritic cell subsets upon intrinsic and extrinsic TLR3 stimulation

Author

Garcias López, Agnès, Bekiaris, Vasileios, Müller Luda, Katarzyna, Hütter, Julia, Ulmert, Isabel, Getachew Muleta, Konjit, Nakawesi, Joy, Kotarsky, Knut, Malissen, Bernard, O'Keeffe, Meredith, Holzmann, Bernhard, Winston Agace, William, Lahl, Katharina, Garcias López, Agnès, Bekiaris, Vasileios, Müller Luda, Katarzyna, Hütter, Julia, Ulmert, Isabel, Getachew Muleta, Konjit, Nakawesi, Joy, Kotarsky, Knut, Malissen, Bernard, O'Keeffe, Meredith, Holzmann, Bernhard, Winston Agace, William, and Lahl, Katharina

Abstract

Initiation of adaptive immunity to particulate antigens in lymph nodes largely depends on their presentation by migratory dendritic cells (DCs). DC subsets differ in their capacity to induce specific types of immunity, allowing subset-specific DC-targeting to influence vaccination and therapy outcomes. Faithful drug design, however, requires exact understanding of subset-specific versus global activation mechanisms. cDC1, the subset of DCs that excel in supporting immunity toward viruses, intracellular bacteria, and tumors, express uniquely high levels of the pattern recognition receptor TLR3. Using various murine genetic models, we show here that both, the cDC1 and cDC2 subsets of cDCs are activated and migrate equally well in response to TLR3 stimulation in a cell extrinsic and TNF-α dependent manner, but that cDC1 show a unique requirement for type I interferon signaling. Our findings reveal common and differing pathways regulating DC subset migration, offering important insights for the design of DC-based vaccination and therapy approaches.

Published
2020

8. Migration of murine intestinal dendritic cell subsets upon intrinsic and extrinsic TLR3 stimulation

Author

Garcias López, Agnès, primary, Bekiaris, Vasileios, additional, Müller Luda, Katarzyna, additional, Hütter, Julia, additional, Ulmert, Isabel, additional, Getachew Muleta, Konjit, additional, Nakawesi, Joy, additional, Kotarsky, Knut, additional, Malissen, Bernard, additional, O'Keeffe, Meredith, additional, Holzmann, Bernhard, additional, Winston Agace, William, additional, and Lahl, Katharina, additional

Published
2020
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9. Migration of intestinal dendritic cell subsets upon intrinsic and extrinsic TLR3 stimulation

Author

Agnès Garcias López, Isabel Ulmert, Julia Hütter, Katarzyna Müller Luda, Vasileios Bekiaris, Bernhard Holzmann, Joy Nakawesi, Bernard Malissen, Katharina Lahl, William W. Agace, Konjit Getachew Muleta, Meredith O'Keeffe, and Knut Kotarsky

Subjects
medicine.anatomical_structure, Immunity, Interferon, Genetic model, Cell, TLR3, Pattern recognition receptor, medicine, Dendritic cell, Biology, Acquired immune system, medicine.drug, Cell biology
Abstract

Initiation of adaptive immunity to particulate antigens in lymph nodes largely depends on their presentation by migratory dendritic cells (DCs). DC subsets differ in their capacity to induce specific types of immunity, allowing subset-specific DC-targeting to influence vaccination and therapy outcomes. Faithful drug design however requires exact understanding of subset-specific versus global activation mechanisms. cDC1, the subset of DCs that excel in supporting immunity towards viruses, intracellular bacteria and tumors, express uniquely high levels of the pattern recognition receptor TLR3. Using various genetic models, we show here that both the cDC1 and cDC2 subsets of cDCs are activated and migrate equally well in response to TLR3 stimulation in a cell extrinsic and TNFα dependent manner, but that cDC1 show a unique requirement for type I interferon signaling. Our findings reveal common and differing pathways regulating DC subset migration, offering important insights for the design of DC-based vaccination and therapy approaches.

Published
2019

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