Article
Oncology
Melissa Prat, Kimberley Coulson, Clement Blot, Godefroy Jacquemin, Mathilde Romano, Marie-Laure Renoud, Mohamad AlaEddine, Augustin Le Naour, Helene Authier, Mouna Chirine Rahabi, Khaddouj Benmoussa, Marie Salon, Melissa Parny, Jean-Pierre Delord, Gwenael Ferron, Lise Lefevre, Bettina Couderc, Agnes Coste
Summary: In this study, it was found that activation of PPARγ in treated small peritoneal macrophages can inhibit ovarian adenocarcinoma growth, regulate the proportion of immune cells, and attenuate the immunosuppressive properties of tumor-associated macrophages.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Michael Chiorazzi, Jan Martinek, Bradley Krasnick, Yunjiang Zheng, Keenan J. Robbins, Rihao Qu, Gabriel Kaufmann, Zachary Skidmore, Melani Juric, Laura A. Henze, Frederic Brosecke, Adam Adonyi, Jun Zhao, Liang Shan, Esen Sefik, Jacqueline Mudd, Ye Bi, S. Peter Goedegebuure, Malachi Griffith, Obi Griffith, Abimbola Oyedeji, Sofia Fertuzinhos, Rolando Garcia-Milian, Daniel Boffa, Frank Detterbeck, Andrew Dhanasopon, Justin Blasberg, Benjamin Judson, Scott Gettinger, Katerina Politi, Yuval Kluger, Karolina Palucka, Ryan C. Fields, Richard A. Flavell
Summary: Researchers developed an autologous system using patient-derived bone marrow cells to establish a genetically matched tumor microenvironment model in mice, which can be used for studying tumor-immune interactions and preclinical drug testing.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Si-Yu Wu, Yi Xiao, Jin-Li Wei, Xiao-En Xu, Xi Jin, Xin Hu, Da-Qiang Li, Yi-Zhou Jiang, Zhi-Ming Shao
Summary: This study identified two distinct microenvironment phenotypes, 'inflamed' and 'non-inflamed', within the classic basal-like subtype of TNBC, and revealed that MYC amplification and overexpression led to the formation of the non-inflamed TIME. Combination therapy with a DNA methyltransferase inhibitor and immunotherapy reversed T cell exhaustion and improved T cell function, resulting in potent antitumor activity in MYC-overexpressing TNBC.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Matthew R. Woeste, Rejeena Shrestha, Anne E. Geller, Shu Li, Diego Montoya-Durango, Chuanlin Ding, Xiaoling Hu, Hong Li, Aaron Puckett, Robert A. Mitchell, Traci Hayat, Min Tan, Yan Li, Kelly M. McMasters, Robert C. G. Martin, Jun Yan
Summary: This study investigates the combination therapy of IRE and beta-glucan in the treatment of pancreatic cancer, and finds that this combination can enhance immune response, reduce tumor burden, and prolong survival in patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Georgia M. Beasley, Michael C. Brown, Norma E. Farrow, Karenia Landa, Rami N. Al-Rohil, Maria Angelica Selim, Aaron D. Therien, Sin-Ho Jung, Junheng Gao, David Boczkowski, Eda K. Holl, April K. S. Salama, Darell D. Bigner, Matthias Gromeier, Smita K. Nair
Summary: In patients with melanoma, those who had intratumoral inflammation and immune cell infiltrates after anti-PD-1 therapy and lerapolturev treatment had a longer progression-free survival, and they also exhibited stronger immune responses in peripheral blood.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Marine Monnier, Lea Paolini, Emeline Vinatier, Alberto Mantovani, Yves Delneste, Pascale Jeannin
Summary: This review article lists the biological differences between human and mouse macrophages and explains the different efficacy of anti-tumor strategies targeting tumor-associated macrophages (TAMs) between human and animal studies. The article points out that differences in the impact of survival and polarization factors, the cytokines produced and markers expressed by TAMs, as well as the limitations of extrapolations based on in vitro models of TAM-like generation need to be considered to improve the design and efficacy of anti-tumor drugs targeting TAMs.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Immunology
Benjamin Ruf, Bernd Heinrich, Tim F. Greten
Summary: Immune-based therapies, particularly immune checkpoint inhibitors, have shown significant improvements in the treatment of hepatocellular carcinoma (HCC), but durable responses are limited to a subset of patients. Understanding the immunologic mechanisms shaping the unique tumor microenvironment of liver cancer is crucial for developing effective therapeutic strategies. Current research focuses on targeting immune cells within the liver to enhance the therapeutic potential of immunotherapeutic agents.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Review
Immunology
Sarah Jaboury, Kenny Wang, Kim Maree O'Sullivan, Joshua Daniel Ooi, Gwo Yaw Ho
Summary: Neutrophil Extracellular Traps (NETs) are a form of pro-inflammatory cell death characterized by the release of DNA webs containing bactericidal enzymes. NETosis plays a role in autoimmune diseases and cancer, causing tissue damage and promoting tumor growth. This mini-review summarizes the interaction between neutrophils, particularly NETosis, and cancer cells, highlighting potential targets for cancer treatment.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Bernd Heinrich, Firouzeh Korangy
Summary: Innate lymphoid cells (ILCs) are a heterogeneous population of the innate immune system that play a crucial role in maintaining immune homeostasis. They exhibit high plasticity, allowing them to quickly respond to changes in their microenvironment. ILCs can transdifferentiate into different subsets in the tumor microenvironment, influencing the immune response and tumor therapy. This review summarizes the functional and plastic heterogeneity of ILCs in homeostasis and disease, with a focus on tumor-driven plasticity and the impact of ILC-induced inflammation on the tumor microenvironment and anti-tumor immunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Alan Herbert, Siddharth Balachandran
Summary: Cancer-associated fibroblasts (CAFs) are a heterogeneous population of cells that promote tumor growth. Among them, inflammatory CAFs (iCAFs) create an immunosuppressive environment but are vulnerable to cell death triggered by interferon-induced ZNA binding protein 1 (ZBP1). Exploiting this vulnerability offers new hope for improved clinical outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Vincenzo Graziano, Andreas Dannhorn, Heather Hulme, Kate Williamson, Hannah Buckley, Saadia A. Karim, Matthew Wilson, Sheng Y. Lee, Brajesh P. Kaistha, Sabita Islam, James E. D. Thaventhiran, Frances M. Richards, Richard Goodwin, Rebecca Brais, Jennifer P. Morton, Simon J. Dovedi, Alwin G. Schuller, Jim Eyles, Duncan Jodrell
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to its ability to evade the immune system and resist immuno-oncology therapies (IOT) through the adenosine pathway, which generates extracellular adenosine (eAdo).
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Shih-Hsun Chen, Pawel K. Dominik, Jessica Stanfield, Sheng Ding, Wenjing Yang, Nadia Kurd, Ryan Llewellyn, Jonathan Heyen, Carole Wang, Zea Melton, Thomas Van Blarcom, Kevin C. Lindquist, Javier Chaparro-Riggers, Shahram Salek-Ardakani
Summary: The study developed a novel affinity-tuned bispecific antibody targeting CD47 and PD-L1 to antagonize innate and adaptive immune checkpoint pathways. This antibody showed enhanced selectivity in the tumor microenvironment and improved therapeutic window compared to monotherapies or combination therapies with alpha CD47 and alpha PD-L1. The bispecific treatment uniquely modulated myeloid and T cells, providing potential for clinical development to improve patient outcomes over current PD-(L)1 and CD47-targeted therapies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Danka Cholujova, Gabor Beke, Zachary R. Hunter, Teru Hideshima, Ludmila Flores, Tatiana Zeleznikova, Denisa Harrachova, Lubos Klucar, Merav Leiba, Lubos Drgona, Steven P. Treon, Efstathios Kastritis, David M. Dorfman, Kenneth C. Anderson, Jana Jakubikova
Summary: By using mass cytometry, this study characterized the immunophenotypic changes in Waldenstrom macroglobulinemia (WM) and revealed the modulation of immune cells by immune checkpoints. It was found that the response to treatment strategies in WM can be monitored by observing the changes in immune cells.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Oncology
Sho Hangai, Yoshitaka Kimura, Tadatsugu Taniguchi, Hideyuki Yanai
Summary: Innate receptors involved in signal transduction play essential roles in regulating tumor immunity, making them potential targets for effective cancer immunotherapy.
Review
Pathology
Laura Maiorino, Juliane Dassler-Plenker, Lijuan Sun, Mikala Egeblad
Summary: Chronic inflammation increases the risk of various cancers, while tumors themselves can trigger an inflammatory response. Inflammation can directly impact tumor growth and influence adaptive immune responses. Innate immune cells exhibit heterogeneity and plasticity, with variable phenotypes depending on tumor type, stage, and treatment options.
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE
(2022)
Article
Oncology
Antonio Tapia-Galisteo, Inigo Sanchez Rodriguez, Oscar Aguilar-Sopena, Seandean Lykke Harwood, Javier Narbona, Mariola Ferreras Gutierrez, Rocio Navarro, Laura Martin-Garcia, Cesareo Corbacho, Marta Compte, Javier Lacadena, Francisco J. Blanco, Patrick Chames, Pedro Roda-Navarro, Luis Alvarez-Vallina, Laura Sanz
Summary: In this study, a novel trispecific T-cell recruiting antibody was developed for the treatment of colorectal cancer, which showed improved efficacy and enhanced tumor selectivity.
Article
Oncology
Belen Blanco, Angel Ramirez-Fernandez, Clara Bueno, Lidia Argemi-Muntadas, Patricia Fuentes, Oscar Aguilar-Sopena, Francisco Gutierrez-Aguera, Samanta Romina Zanetti, Antonio Tapia-Galisteo, Laura Diez-Alonso, Alejandro Segura-Tudela, Maria Castella, Berta Marzal, Sergi Betriu, Seandean L. Harwood, Marta Compte, Simon Lykkemark, Ainhoa Erce-Llamazares, Laura Rubio-Perez, Anais Jimenez-Reinoso, Carmen Dominguez-Alonso, Maria Neves, Pablo Morales, Estela Paz-Artal, Sonia Guedan, Laura Sanz, Maria L. Toribio, Pedro Roda-Navarro, Manel Juan, Pablo Menendez, Luis Alvarez-Vallina
Summary: This study compares the efficacy of CAR-T19 cells and STAb-T19 cells and finds that STAb-T19 cells are more effective in inducing cytotoxicity, avoiding leukemia escape, and preventing relapse. CAR-T19 cells induce leukemia escape through rapid CD19 internalization and degradation, while STAb-T19 cells prevent CD19 downmodulation by forming canonical immunologic synapses. In a long-term patient-derived xenograft mouse model, STAb-T19 cells efficiently eradicate leukemia cells, while leukemia relapse occurs after CAR-T19 therapy.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Multidisciplinary Sciences
Oana Hangiu, Marta Compte, Anders Dinesen, Rocio Navarro, Antonio Tapia-Galisteo, Ole A. Mandrup, Ainhoa Erce-Llamazares, Rodrigo Lazaro-Gorines, Daniel Nehme-Alvarez, Carmen Dominguez-Alonso, Seandean L. Harwood, Carlos Alfonso, Belen Blanco, Laura Rubio-Perez, Anais Jimenez-Reinoso, Laura Diez-Alonso, Francisco J. Blanco, Laura Sanz, Kenneth A. Howard, Luis Alvarez-Vallina
Summary: This study introduces bispecific antibodies fused with human and mouse sequences that specifically target the tumor microenvironment to provide 4-1BB costimulation. These antibodies show specific targeting of the tumor cells and provide costimulatory activity, with prolonged circulatory half-life and tumor inhibition effects. Combining these antibodies with PD-1-blocking antibodies enhances the therapeutic effect.
Review
Medicine, Research & Experimental
Antonio Tapia-Galisteo, Marta Compte, Luis alvarez-Vallina, Laura Sanz
Summary: Multispecific antibodies have the potential to overcome current limitations and have important implications in cancer therapy.
Article
Medicine, Research & Experimental
Ana Antunes, Luis Alvarez-Vallina, Federico Bertoglio, Nicolas Bouquin, Stephanie Cornen, Francis Duffieux, Pierre Ferre, Raphaelle Gillet, Christian Jorgensen, Mark B. Leick, Bernard Maillere, Helene Negre, Mireia Pelegrin, Nicolas Poirier, Dietmar Reusch, Bruno Robert, Guy Serre, Alain Vicari, Martin Villalba, Christoph Volpers, Gavin Vuddamalay, Herve Watier, Thierry Wurch, Lennart Zabeau, Stefan Zielonka, Baolin Zhang, Alain Beck, Pierre Martineau
Summary: The annual Antibody Industrial Symposium brought together scientists from academia and industry to discuss new advancements in antibody engineering and cell-based therapies. The symposium also addressed production and intellectual property protection issues.
Article
Oncology
Laura Rubio-Perez, Rodrigo Lazaro-Gorines, Seandean L. Harwood, Marta Compte, Rocio Navarro, Antonio Tapia-Galisteo, Jaume Bonet, Belen Blanco, Simon Lykkemark, Angel Ramirez-Fernandez, Mariola Ferreras-Gutierrez, Carmen Dominguez-Alonso, Laura Diez-Alonso, Alejandro Segura-Tudela, Oana Hangiu, Ainhoa Erce-Llamazares, Francisco J. Blanco, Cruz Santos, Jose L. Rodriguez-Peralto, Laura Sanz, Luis Alvarez-Vallina
Summary: In this study, a PD-L1/EGFR symmetric bispecific antibody was developed, which could simultaneously inhibit EGFR-mediated proliferation, effectively block PD-1/PD-L1 interaction, and induce strong antigen-specific antibody-dependent cellular cytotoxicity activity in vitro. Potent therapeutic efficacies of this antibody were observed in two different humanized mouse models.
Review
Oncology
Antonio Tapia-Galisteo, Luis alvarez-Vallina, Laura Sanz
Summary: Immune cell engagers are modified antibodies that have one arm binding a tumor-associated antigen and another arm binding an activating receptor in immune effector cells. These engagers have the potential to revolutionize the treatment of hematological malignancies and are more potent than conventional monoclonal antibodies. The field is growing rapidly, with multiple formats and targets currently in clinical trials, and trispecific antibodies show even more promise by targeting additional tumor-associated antigens or costimulatory receptors.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Rodrigo Lazaro-Gorines, Patricia Perez, Ignacio Heras-Murillo, Irene Adan-Barrientos, Guillermo Albericio, David Astorgano, Sara Flores, Joanna Luczkowiak, Nuria Labiod, Seandean L. Harwood, Alejandro Segura-Tudela, Laura Rubio-Perez, Yudhi Nugraha, Xiaoran Shang, Yuxing Li, Carlos Alfonso, Kaylin A. Adipietro, Dinendra L. Abeyawardhane, Rocio Navarro, Marta Compte, Wenbo Yu, Alexander D. Mackerell, Laura Sanz, David J. Weber, Francisco J. Blanco, Mariano Esteban, Edwin Pozharski, Raquel Godoy-Ruiz, Ines G. Munoz, Rafael Delgado, David Sancho, Juan Garcia-Arriaza, Luis Alvarez-Vallina
Summary: In this study, a broadly neutralizing antibody (nAb) TNT was generated, which showed high-avidity neutralizing interaction by simultaneously binding to all six RBD epitopes. By fusing an anti-DNGR-1 scFv to TNT, a bispecific trimerbody TN(T)DNGR-1 was generated, which targeted neutralized virions to cDC1s and promoted T cell cross-priming. Therapeutic administration of TN(T)DNGR-1 protected mice from lethal SARS-CoV-2 infection and enhanced virus-specific humoral and CD8(+) T cell responses.
Article
Biochemistry & Molecular Biology
Javier Narbona, Luisa Hernandez-Baraza, Ruben G. Gordo, Laura Sanz, Javier Lacadena
Summary: Immunotoxins are chimeric molecules that combine the specificity of an antibody-based targeting domain and the cytotoxic potency of a toxin. This study designed and characterized several immunotoxin constructs using nanobodies as targeting domains against EGFR. The results confirm the therapeutic potential of a-sarcin-based nanoITXs.