Review
Biochemistry & Molecular Biology
Rodrigo C. C. De Marco, Hector J. J. Monzo, Paivi M. Ojala
Summary: With the continuous advancements in immunotherapy and precision medicine, adoptive cell therapy (ACT) has emerged as a new treatment approach in oncology. Chimeric antigen receptor (CAR) T cells, genetically modified lymphocytes, have shown promising results in targeting and killing cancer cells. Commercialization of CAR T cell therapy has paved the way for future bright developments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Rui Zheng, Yuankun Chen, Yiting Zhang, Sixin Liang, Xiaojuan Zhao, Yiyi Wang, Pengju Wang, Ruotong Meng, Angang Yang, Bo Yan
Summary: Our study explores the effect of low-affinity CARs using humanized scFvs on the function of CAR-T cells. We find that moderately reducing the affinity of CARs can maintain anti-tumor efficacy and improve the safety of CAR therapy both in vitro and in vivo. In addition, T cells expressing the VL domain only antibody show long-lasting tumor elimination capability and lower cytokine levels.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Nattaporn Phanthaphol, Chalermchai Somboonpatarakun, Kwanpirom Suwanchiwasiri, Thaweesak Chieochansin, Jatuporn Sujjitjoon, Sopit Wongkham, John Maher, Mutita Junking, Pa-thai Yenchitsomanus
Summary: CAR T cell therapy has shown efficacy in hematologic malignancies, but further investigation is needed for its application in solid tumors. The selection of target antigens highly expressed in cancer cells but not normal cells is crucial for successful immunotherapy.
FRONTIERS IN ONCOLOGY
(2021)
Review
Immunology
Peng Zhang, Yang Zhang, Nan Ji
Summary: Glioblastoma (GBM) is a deadly brain cancer with limited efficacy of standard treatments, necessitating the development of new therapies. Chimeric antigen receptor T (CAR-T) cell immunotherapy has shown success in hematological malignancies, but has not yet yielded promising results in GBM. CAR-T cell therapy for GBM faces challenges including tumor heterogeneity, immunosuppressive microenvironment, and cell persistence.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Elien De Bousser, Nico Callewaert, Nele Festjens
Summary: T cell-engaging immunotherapy aims to activate cytotoxic T cells to destroy cancer cells, while CAR T cell therapy redirects immune cells to recognize tumor antigens. Despite success, challenges such as toxicities and limited efficacy need to be addressed for the broad use of CAR T cell therapy. Research is ongoing to develop more powerful CAR T cells.
Article
Oncology
Sophia Stock, Mohamed-Reda Benmebarek, Anna-Kristina Kluever, Diana Darowski, Christian Jost, Kay-Gunnar Stubenrauch, Joerg Benz, Anne Freimoser-Grundschober, Ekkehard Moessner, Pablo Umana, Marion Subklewe, Stefan Endres, Christian Klein, Sebastian Kobold
Summary: This study developed a P329G-directed CAR T cell that can selectively bind with specific mutated antibodies, demonstrating significant in vitro and in vivo effector functions in different types of solid tumor models. This opens up possibilities for further clinical translation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Simone Thomas, Hinrich Abken
Summary: Chimeric antigen receptors (CARs) in the second generation format provide two signals for T cell activation. However, CAR T cell persistence is limited and can be improved by supplementing cytokines as the third signal. Recent progress in understanding receptor signaling allows for the engineering of cytokines to selectively stimulate CAR T cells. We discuss strategies for engineering cytokine help intensified CAR (CHIC) T cells for adoptive cell therapy.
FRONTIERS IN IMMUNOLOGY
(2023)
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)
Review
Oncology
Ross E. Staudt, Robert D. Carlson, Adam E. Snook
Summary: Immunotherapy, using genetically modified T cells to target and eliminate cancer cells, has shown great success in the treatment of hematologic cancers. However, its application in gastrointestinal cancers requires further research and development.
CANCER BIOLOGY & THERAPY
(2022)
Article
Immunology
Karin Teppert, Nora Winter, Vera Herbel, Caroline Brandes, Simon Lennartz, Fabian Engert, Andrew Kaiser, Thomas Schaser, Dominik Lock
Summary: The prognosis for patients with metastatic melanoma is poor and treatment options are limited. However, genetically-engineered T cell therapy targeting CSPG4 shows promise as a potential treatment. Combining a chimeric co-stimulatory receptor (CCR) and a CSPG4-directed chimeric antigen receptor (CAR) enhances the anti-tumor response and provides a new approach for treating metastatic melanoma.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemical Research Methods
Cuilin Zhang, Qiuyu Zhuang, Jingfeng Liu, Xiaolong Liu
Summary: Synthetic biology is an interdisciplinary research area that uses engineering principles to design and construct biological systems for practical applications. Chimeric antigen receptor (CAR) T cells, as one of the most successful clinical applications of synthetic biology, have shown tremendous success in treating blood malignancies. However, there are still limitations to CAR T cell therapy, hence the need for innovative CAR design becomes urgent.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Oncology
P. Connor Johnson, Caron Jacobson, Alisha Yi, Mahmoud R. Gaballa, Nora Horick, Dustin J. Rabideau, Kevin Lindell, Gabriel D. DePinho, Areej R. El-Jawahri, Matthew J. Frigault
Summary: A retrospective analysis of 235 patients receiving CAR T-cell therapy found that bridging therapy use was not associated with differences in overall response, complete response rate, or progression-free survival, but was associated with worse overall survival. Additional poor prognostic factors may contribute to this association, highlighting the need for innovative bridging therapy regimens for these patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Kevin Pan, Hizra Farrukh, Veera Chandra Sekhar Reddy Chittepu, Huihong Xu, Chong-xian Pan, Zheng Zhu
Summary: CAR immunotherapy has achieved significant progress in hematological malignancies, but faces challenges in solid tumors. CAR NK cells and CAR macrophages have advantages and limitations. Developing CAR macrophages could be a strategy to overcome hurdles associated with CAR therapy in solid tumors.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Taewoong Choi, Yubin Kang
Summary: Although treatment outcomes for multiple myeloma patients have greatly improved in the past two decades, the disease remains incurable. New immunotherapies, including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy, have emerged to treat multiple myeloma. This article provides a comprehensive review of the clinical efficacy, safety, and potential resistance mechanisms of current myeloma CAR-T therapies, with a focus on B Cell Maturation Antigen (BCMA) as the most successful target. The article also discusses novel strategies to enhance the effectiveness of myeloma CAR-T therapy.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Neurosciences
Lisa Feldman, Christine Brown, Behnam Badie
Summary: Glioblastoma is the most common and aggressive primary brain tumor in adults, and current mainstay treatments are ineffective, leading to the development of immunotherapy strategies. CAR T cell therapy uses genetically modified T cells to target tumor-associated antigens and has the potential to destroy tumor cells.
NEUROMOLECULAR MEDICINE
(2022)
Article
Nanoscience & Nanotechnology
Greter A. Ortega, S. Del Sol-Fernandez, Yadileiny Portilla, Enrique Cedeno, Edilso Reguera, Seshasai Srinivasan, Domingo F. Barber, Ernesto Marin, Amin Reza Rajabzadeh
Summary: Novel rodlike CdTe@MPA-PDA particles loaded with CdTe quantum dots and polydopamine have unique chemical features and show potential as an actuator for photothermal therapy and oxidative stress induction. These particles interact with cancer cells, induce oxidative stress, and enhance apoptosis, demonstrating their effectiveness as a photothermal agent with subcellular localization capabilities.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Review
Immunology
Vladimir Mulens-Arias, Jose Manuel Rojas, Domingo F. Barber
Summary: The synthesis and functionalization of iron oxide nanoparticles have sparked interest in studying them as theranostic agents, particularly in the field of cancer immunotherapy. Understanding the effects of IONPs on the immune system is crucial, as they may impact immune cell responses through various mechanisms. Furthermore, harnessing the properties of IONPs could lead to the development of innovative therapies for cancer treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Engineering, Biomedical
Yadileiny Portilla, Vladimir Mulens-Arias, Alberto Paradela, Antonio Ramos-Fernandez, Sonia Perez-Yague, M. Puerto Morales, Domingo F. Barber
Summary: This study investigated the intracellular transit of two magnetic nanoparticles (MNPs) with different surface coatings in mouse cell lines. The results showed that the coating type influenced the intracellular trafficking rate and the nature of the endolysosomes in macrophages. The MNPs with a specific coating had a slower transit rate and resulted in endolysosomes with more lytic enzymes and catalytic proteins in macrophages. These MNPs also induced more autophagic vesicles and enhanced the expression of iron metabolism-related genes and proteins.
Review
Microbiology
Jose M. Rojas, Veronica Martin, Noemi Sevilla
Summary: Bluetongue virus (BTV) is an economically important disease in ruminants, typically transmitted by Culicoides spp. Some BTV strains can also be transmitted vertically, leading to fetal malformations and abortions. The factors associated with the virus potency to cross the placental barrier are not well defined.
Article
Biotechnology & Applied Microbiology
Marta L. DeDiego, Yadileiny Portilla, Neus Daviu, Dario Lopez-Garcia, Laura Villamayor, Vladimir Mulens-Arias, Jesus G. Ovejero, Alvaro Gallo-Cordova, Sabino Veintemillas-Verdaguer, M. Puerto Morales, Domingo F. Barber
Summary: This study analyzed the potential of using iron oxide nanoparticles to treat and prevent SARS-CoV-2 infection. The nanoparticles were found to impair virus replication and transcription, both before and after infection, and SARS-CoV-2 infection was found to affect cellular iron metabolism. These findings suggest that the nanoparticles may be repurposed as prophylactic or therapeutic treatments for SARS-CoV-2 infection.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Virology
Daniel Rodriguez-Martin, Isabel Garcia-Garcia, Veronica Martin, Jose Manuel Rojas, Noemi Sevilla
Summary: Viruses, including morbilliviruses, can impair immunity through various strategies. In this study, it was found that the highly contagious morbillivirus peste des petits ruminants virus (PPRV) can infect monocytes and dendritic cells (DC), leading to immunosuppression. PPRV infection compromised the differentiation and phagocytic ability of monocyte-derived DC, as well as their capacity to activate T cell responses. Furthermore, PPRV-infected DC exhibited an immunosuppressive profile. These findings contribute to our understanding of how morbilliviruses suppress the immune response.
JOURNAL OF VIROLOGY
(2022)
Article
Immunology
Jose M. Rojas, Carolina Mancho, Andres Louloudes-Lazaro, Daniel Rodriguez-Martin, Miguel Avia, Santiago Moreno, Noemi Sevilla, Veronica Martin
Summary: This study investigates the immunomodulatory properties of OX40L and CD70 on the immune response to OVA antigen. The results show that OaCD70 administration can enhance the adaptive immune response to OVA, including increased antibody titers and the number of antigen-specific IgG-secreting B cells. Additionally, OaCD70 also promotes the differentiation and long-term activity of CD8(+) T cell effectors.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Yadileiny Portilla, Yilian Fernandez-Afonso, Sonia Perez-Yague, Vladimir Mulens-Arias, M. Puerto Morales, Lucia Gutierrez, Domingo F. Barber
Summary: This study analyzed the biodistribution, organ accumulation and degradation of different coatings of iron oxide magnetic nanoparticles (MNPs) in vivo. The results showed that the coating influenced the proportion of MNPs in different organs, with faster degradation in the liver regardless of the coating. This information is important for choosing the optimal coating for specific biomedical applications.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Immunology
Pedro J. Alcolea, Jaime Larraga, Daniel Rodriguez-Martin, Ana Alonso, Francisco J. Loayza, Jose M. Rojas, Silvia Ruiz-Garcia, Andres Louloudes-Lazaro, Ana B. Carlon, Pedro J. Sanchez-Cordon, Pablo Nogales-Altozano, Natalia Redondo, Miguel Manzano, Daniel Lozano, Jesus Palomero, Maria Montoya, Maria Vallet-Regi, Veronica Martin, Noemi Sevilla, Vicente Larraga
Summary: Researchers presented a promising DNA vaccine candidate, pPAL-Sfs + pPAL-N, which demonstrated strong protective effects in mice, fully controlling viral replication and inducing potent humoral and cellular immune responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Vladimir Mulens-Arias, Yadileiny Portilla, Sonia Perez-Yaguee, Raquel Ferreras-Martin, M. Elena Martin, Victor M. Gonzalez, Domingo F. Barber
Summary: Triple-negative breast cancer (TNBC) is a difficult subtype to treat and overactivation of MNK1 has been associated with tumor aggressiveness. This study showed that polyethyleneimine-coated iron oxide nanoparticles (PEI-IONPs) could enhance the intracellular delivery of an MNK1-specific aptamer, resulting in reduced MNK1 signaling and inhibiting TNBC cell migration in vitro. However, the antitumor effect of the aptamer-PEI-IONP complex was compromised in vivo due to minimal accumulation of IONPs in the tumor.
CANCER NANOTECHNOLOGY
(2023)
Article
Nanoscience & Nanotechnology
David Egea-Benavente, Carlos Diaz-Ufano, Alvaro Gallo-Cordova, Francisco Javier Palomares, Jhon Lehman Cuya Huaman, Domingo F. Barber, Maria del Puerto Morales, Jeyadevan Balachandran
Summary: This work analyzes the formation mechanism of cubic magnetic iron oxide mesocrystals by thermal decomposition in organic media, finding a nonclassical pathway via the attachment of crystallographically aligned primary cubic particles and sintering to achieve a sizable single crystal. The solvent 1-octadecene and the surfactant agent biphenyl-4-carboxylic acid are key parameters. The degree of aggregation of the cores forming the final particle strongly affects the magnetic properties and hyperthermia efficiency.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Nanoscience & Nanotechnology
Yadileiny Portilla, Vladimir Mulens-Arias, Neus Daviu, Alberto Paradela, Sonia Perez-Yague, Domingo F. Barber
Summary: When iron oxide nanoparticles (IONPs) come into contact with biological fluids, they form protein corona complexes that vary in composition based on the origin of the serum. These complexes have an impact on the interaction between IONPs and macrophages, ultimately affecting the immune system.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Immunology
Andres Paris-Munoz, Gonzalo Aizpurua, Domingo F. Barber
Summary: This study revealed the absence of CD8(+) regulatory T cells in two lupus-prone mouse models, MRL/MPJ and MRL/lpr, compared to a non-prone mouse strain, C57BL/6. The findings suggest that Helios plays a regulatory role in the pathogenesis of lupus and its expression profile is altered in other relevant T cell populations.
FRONTIERS IN IMMUNOLOGY
(2022)
Meeting Abstract
Immunology
Andres Paris, Domingo F. Barber
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Jose M. Rojas, Elena Pascual, Sean R. Wattegedera, Miguel Avia, Cesar Santiago, Veronica Martin, Gary Entrican, Noemi Sevilla
Summary: This study characterized the role of TLR2 in the immune response to PPRV, showing that PPRV induces IL-8 production through TLR2 activation by viral protein H. The interaction of H with TLR2 also activates ERK signaling and stimulates the secretion of pro-inflammatory cytokines in primary ovine dendritic cells.