Article
Oncology
Rosa Nguyen, Xiyuan Zhang, Ming Sun, Shahroze Abbas, Charlie Seibert, Michael C. Kelly, Jack F. Shern, Carol J. Thiele
Summary: In this study, two new immunocytokines (IC) were developed by linking IL15 and IL21 to hu14.18 for the treatment of GD2-expressing neuroblastoma. Compared to hu14.18-IL2, hu14.18-IL15 and-IL21 showed better preclinical activity, warranting further consideration for clinical testing.
CLINICAL CANCER RESEARCH
(2022)
Review
Immunology
Paul Shafer, Lauren M. Kelly, Valentina Hoyos
Summary: This article presents a review of the use of engineered T cells for cancer therapy. The mechanisms of T cell antigen recognition and signal transduction mediated through CARs and TCRs are discussed, along with the current classes of cancer antigens recognized by TCR T therapies and pre-clinical strategies for TCR discovery and enhancement. The current landscape of clinical trials for TCR T therapy is also reviewed, providing insights into the development of future engineered TCR approaches.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Wesley Huisman, Ilse Gille, Lieve E. van der Maarel, Lois Hageman, Laura T. Morton, Rob C. M. de Jong, Mirjam H. M. Heemskerk, Derk Amsen, J. H. Frederik Falkenburg, Inge Jedema
Summary: In this study, we isolated the first functional HLA-A*01:01-restricted EBV-LMP2-specific T-cell populations and TCRs and demonstrated that these T-cell populations and T cells modified to express the LMP2-specific T-cell receptor showed IFN-gamma secretion and cytotoxicity toward EBV-LMP2-expressing malignant cell lines.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Immunology
Maria Vono, Beatris Mastelic-Gavillet, Elodie Mohr, Malin Ostensson, Josefine Persson, Thorunn A. Olafsdottir, Sylvain Lemeille, David Pejoski, Oliver Hartley, Dennis Christensen, Peter Andersen, Arnaud M. Didierlaurent, Ali M. Harandi, Paul-Henri Lambert, Claire-Anne Siegrist
Summary: C-type lectin receptor (CLR) agonists have been found to be more effective than Toll-like receptor (TLR) agonists in inducing primary B cell responses in early life. This study investigates the mechanisms behind the difference in neonatal adjuvanticity between CLR-based (CAF(R)01) and TLR4-based (GLA-SE) adjuvants. The results demonstrate that CAF01 induces mixed Th1/Th17 neonatal responses and Tfh cells that are crucial for germinal center formation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Mikiya Tsunoda, Hiroyasu Aoki, Haruka Shimizu, Shigeyuki Shichino, Kouji Matsushima, Satoshi Ueha
Summary: Temporal analysis of T cell receptor (TCR) repertoire is important for monitoring changes in antigen-specific T cells in cancer patients. However, lack of experimental models for temporal analysis within a homogeneous population limits understanding of the relationship between TCR repertoire changes and antitumor responses. Bilateral tumor model showed highly similar T-cell clones in bilateral tumors and different patterns in draining lymph nodes, suggesting independent induction of tumor-reactive T cell clones in each lymph node.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Xiangjun Liu, Shanzhao Jin, Simeng Hu, Ruoyan Li, Haihao Pan, Yi Liu, Pan Lai, Deshu Xu, Jingru Sun, Ziyang Liu, Yumei Gao, Yifan Zhao, Fengjie Liu, Yu Xiao, Yingyi Li, Yujie Wen, Zhuojing Chen, Bufang Xu, Yuchieh Lin, Menglong Ran, Qianxi Li, Shuxia Yang, Hang Li, Ping Tu, Muzlifah Haniffa, Sarah A. Teichmann, Fan Bai, Yang Wang
Summary: Cutaneous T cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphoma characterized by clonal malignant T cells. This study analyzed CTCL patient samples using single-cell RNA-seq, TCR and whole-exome sequencing, revealing the molecular profiles of malignant T cells and their association with the microenvironment and clinical outcomes.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Min Wen Ku, Pierre Authie, Fabien Nevo, Philippe Souque, Maryline Bourgine, Marta Romano, Pierre Charneau, Laleh Majlessi
Summary: Utilizing a lentiviral vector system with a human beta 2-microglobulin promoter, researchers found that the lentiviral-based vaccine outperformed the Ad5 'gold-standard' in mice and rats by inducing a polyfunctional and long-lived immune response.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Saskia J. J. Santegoets, Marij J. P. Welters, Deborah S. S. Schrikkema, Manon R. R. Freriks, Hanna Kok, Bianca Weissbrich, Anouk van den Branden, Carsten Linnemann, Ton N. N. Schumacher, Sabina Adhikary, Gavin Bendle, Sjoerd H. H. van der Burg
Summary: Immunotherapies targeting tumor-specific targets focus on expanding and activating T cells against neoantigens or oncogenic viruses, such as the human papilloma virus type 16 (HPV16). In this study, CD8(+) T cell epitopes in HPV16-induced tumors were identified using multimers and a functional screening platform. Specific HLA-peptide combinations dominated the T cell response in patients expressing these HLA alleles. T cell receptors reactive to HLA class I-restricted peptides could be isolated and shown to have tumor reactivity. These tumor-reactive T cell receptors can potentially be used in adoptive cell transfer approaches for treating HPV16-induced cancers.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Immunology
Suzanne Quinn, Natasha Lenart, Victoria Dronzek, Gina M. Scurti, Nasheed M. Hossain, Michael Nishimura
Summary: Immunotherapy is an effective treatment for cancer, but it only works for a small percentage of patients. Adoptive cell transfer (ACT) is a facet of immunotherapy that involves transferring T cells targeting tumor cells to the patient. The main challenges in ACT are improving clinical responses and reducing adverse events. Current research focuses on identifying novel tumor-targeting T cell receptors, improving safety and efficacy, and combining ACT with other immunotherapies.
Article
Oncology
Brigitte Dreno, Amir Khammari, Agnes Fortun, Virginie Vignard, Soraya Saiagh, Tiffany Beauvais, Nicolas Jouand, Sylvain Bercegay, Sylvain Simon, Francois Lang, Nathalie Labarriere
Summary: The study demonstrated the feasibility and safety of using Melan-A and MELOE-1 specific T cells for ACT in metastatic melanoma patients, but the clinical efficacy can be further enhanced by selecting highly reactive T cells based on PD-1 and TIGIT co-expression and combining with ICI such as anti-PD-1.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Medicine, Research & Experimental
Maria Tristan-Manzano, Noelia Maldonado-Perez, Pedro Justicia-Lirio, Marina Cortijo-Gutierrez, Pablo Tristan-Ramos, Carlos Blanco-Benitez, Kristina Pavlovic, Araceli Aguilar-Gonzalez, Pilar Munoz, Francisco J. Molina-Estevez, Valerie Griesche, Juan Antonio Marchal, Sara R. Heras, Karim Benabdellah, Francisco Martin
Summary: The use of an externally administered inductor to control transgene expression is a promising strategy for improving the safety and effectiveness of gene therapy. Researchers have developed transactivator-free lentiviral vectors (LOP LVs) that respond to doxycycline (Dox), allowing for controlled transgene expression in human stem cells and primary T cells. By inserting an Is2 insulator into the LOP LVs, transgene expression in human primary T cells can be controlled. Inducible CAR-T cells generated using this system selectively kill CD19+ cells in the presence of Dox. This study describes the first transactivator-free system capable of generating Dox-inducible advanced therapy medicinal products (ATMPs).
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Biochemistry & Molecular Biology
Ken-Edwin Aryee, Lisa M. Burzenski, Li-Chin Yao, James G. Keck, Dale L. Greiner, Leonard D. Shultz, Michael A. Brehm
Summary: Human innate immunity, including natural killer (NK) cells, plays a critical role in tumor surveillance and immunoregulation in the tumor microenvironment. Humanized mouse models have been developed to study human immuno-oncology, but the development and survival of human NK cells in these models are limited. Researchers have created a mouse model with constitutive expression of human Interleukin 15 (IL15) to enhance the development of functional human NK cells and limit tumor growth.
Article
Biotechnology & Applied Microbiology
Robert Dixon, Stephen G. Preston, Stefan Dascalu, Patrik G. Flammer, Steven R. Fiddaman, Kirstie McLoughlin, Amy Boyd, Jiri Volf, Ivan Rychlik, Michael B. Bonsall, Bernd Kaspers, Adrian L. Smith
Summary: This study reveals that chicken TCR gamma locus has undergone tandem duplication events that have shaped its evolution. Repertoire sequencing shows large differences in the usage of individual TRGV genes across various tissues, with TRGV3.3 dominating every tissue. The application of repertoire analysis in chickens with a high circulating gamma delta phenotype is important for understanding the functional diversity of these cells and their potential in improving health.
Article
Oncology
Fumihiro Fujiki, Soyoko Morimoto, Yuya Nishida, Satoe Tanii, Nao Aoyama, Miki Inatome, Kento Inoue, Akiko Katsuhara, Hiroko Nakajima, Jun Nakata, Sumiyuki Nishida, Akihiro Tsuboi, Yoshihiro Oka, Yusuke Oji, Shinji Sogo, Haruo Sugiyama
Summary: In this study, a novel platform cell line CD4-2D3 was generated to accurately evaluate the functional avidity of HLA class II-restricted TCRs. By substituting amino acids in CDR3 region of the TCR, the functional avidity of an HLA class II-restricted TCR specific for WT1-derived helper peptide was significantly increased. Transduction of the avidity-maturated TCR resulted in strong cytotoxicity against WT1-expressing leukemia cells on CD4(+) T cells, demonstrating the potential of high avidity TCRs in cancer immunotherapy.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Cell Biology
John C. Charpentier, Philip D. King
Summary: Endocytosis, once primarily viewed as a means to neutralize pathogens or facilitate feeding, is now known to regulate a wide range of eukaryotic cell processes, including signal transduction, mitosis, lipid homeostasis, and directed migration. Various forms of endocytosis play important roles in regulating alpha beta and gamma delta T cell functions, such as T cell receptor signaling, antigen discovery by trogocytosis, and activated cell growth. This article examines the contribution of both clathrin-mediated and clathrin-independent mechanisms of endocytosis to T cell biology.
CELL COMMUNICATION AND SIGNALING
(2021)
Correction
Biochemistry & Molecular Biology
A. Magnani, M. Semeraro, F. Adam, C. Booth, L. Dupre, E. C. Morris, A. Gabrion, C. Roudaut, D. Borgel, A. Toubert, E. Clave, C. Abdo, G. Gorochov, R. Petermann, M. Guiot, M. Miyara, D. Moshous, E. Magrin, A. Denis, F. Suarez, C. Lagresle, A. M. Roche, J. Everett, A. Trinquand, M. Guisset, J. Xu Bayford, S. Hacein-Bey-Abina, A. Kauskot, R. Elfeky, C. Rivat, S. Abbas, H. B. Gaspar, E. Macintyre, C. Picard, F. D. Bushman, A. Galy, A. Fischer, E. Six, A. J. Thrasher, M. Cavazzana
Review
Biochemistry & Molecular Biology
David Escors, Ana Bocanegra, Luisa Chocarro, Ester Blanco, Sergio Pineiro-Hermida, Maider Garnica, Leticia Fernandez-Rubio, Ruth Vera, Hugo Arasanz, Grazyna Kochan
Summary: PD-L1/PD-1 blockade immunotherapy has revolutionized cancer treatment, but its mechanisms and effectiveness are still not fully understood. This article reviews the evidence supporting the role of CD4 T cells in anti-tumor immunity and their potential as predictors of response to PD-L1/PD-1 blockade immunotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Alan Kennedy, Erin Waters, Behzad Rowshanravan, Claudia Hinze, Cayman Williams, Daniel Janman, Thomas A. Fox, Claire Booth, Anne M. Pesenacker, Neil Halliday, Blagoje Soskic, Satdip Kaur, Omar S. Qureshi, Emma C. Morris, Shinji Ikemizu, Christopher Paluch, Jiandong Huo, Simon J. Davis, Emmanuel Boucrot, Lucy S. K. Walker, David M. Sansom
Summary: CD28 and CTLA-4 play important roles in regulating T cell immunity. The study found that CTLA-4 captures ligands through transendocytosis, and CD80 leads to ubiquitination and degradation of CTLA-4, while CD86 allows CTLA-4 to detach and recycle back to the cell surface. Clinically relevant mutations disrupt CD86 transendocytosis and are associated with autoimmune diseases.
Article
Cell Biology
Thomas Andrew Fox, Benjamin Christopher Houghton, Lina Petersone, Erin Waters, Natalie Mona Edner, Alex McKenna, Olivier Preham, Claudia Hinze, Cayman Williams, Adriana Silva de Albuquerque, Alan Kennedy, Anne Maria Pesenacker, Pietro Genovese, Lucy Sarah Kate Walker, Siobhan Oisin Burns, David Michael Sansom, Claire Booth, Emma Catherine Morris
Summary: A gene editing strategy was designed to insert the CTLA-4 cDNA into primary human T cells, restoring CTLA-4 expression and demonstrating the feasibility of using T cell gene therapy for CTLA-4 insufficiency.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Immunology
Mercedes Lachen-Montes, Naroa Mendizuri, Karina Ausin, Miriam Echaide, Ester Blanco, Luisa Chocarro, Maria de Toro, David Escors, Joaquin Fernandez-Irigoyen, Grazyna Kochan, Enrique Santamaria
Summary: One common symptom of COVID-19 is a sudden loss of smell, and the SARS-CoV-2 virus has been detected in the olfactory bulb. By studying the expression of SARS-CoV-2 structural proteins in mouse olfactory bulb cells, researchers have uncovered widespread metabolic remodeling and differential activation dynamics in immune pathways, providing insights into the mechanism behind olfactory inflammation observed in COVID-19 patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Miriam Echaide, Ibone Labiano, Marina Delgado, Angela Fernandez de Lascoiti, Patricia Ochoa, Maider Garnica, Pablo Ramos, Luisa Chocarro, Leticia Fernandez, Hugo Arasanz, Ana Bocanegra, Ester Blanco, Sergio Pineiro-Hermida, Pilar Morente, Ruth Vera, Maria Alsina, David Escors, Grazyna Kochan
Summary: In this study, immune profiling was performed in healthy donors and oncologic patients infected with SARS-CoV-2, BNT162b2-vaccinated, and with previous COVID-19. The findings showed that vaccination induced poor cellular immunity towards the S protein in cancer patients, while natural infection targeted the M and S proteins. Memory T-cell expansion was only observed in vaccinated donors who had previously been diagnosed with COVID-19.
Review
Biochemistry & Molecular Biology
Ester Blanco, Luisa Chocarro, Leticia Fernandez-Rubio, Ana Bocanegra, Hugo Arasanz, Miriam Echaide, Maider Garnica, Sergio Pineiro-Hermida, Grazyna Kochan, David Escors
Summary: Immunotherapies based on immune checkpoint blockade have shown promising clinical outcomes but lack efficacy in most cancer patients. Intratumor delivery of monoclonal antibodies (mAbs) has emerged as a potential solution to reduce adverse events and improve treatment efficacy. Gene therapy vectors expressing mAbs inside tumors offer an attractive approach for local intratumor delivery. This expanding research subject will likely play a key role in future oncology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Luisa Chocarro, Ester Blanco, Leticia Fernandez-Rubio, Hugo Arasanz, Ana Bocanegra, Miriam Echaide, Maider Garnica, Pablo Ramos, Sergio Pineiro-Hermida, Ruth Vera, Grazyna Kochan, David Escors
Summary: Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment for cancer, particularly in hematological malignancies. However, its efficacy in solid tumors is limited due to the immunosuppressive tumor microenvironment (TME) that inactivates engineered T cells. Myeloid lineage (M) cells in the TME are highly immunosuppressive and interact with other immune cells, leading to immunosuppression and angiogenesis. CAR-M cell therapy has emerged as a potential immunotherapy strategy to enhance the efficacy, survival, persistence, and safety of CAR treatments in solid tumors. However, the mechanisms of CAR-M action and their impact on the TME are still poorly understood.
Review
Biochemistry & Molecular Biology
Hugo Arasanz, Luisa Chocarro, Leticia Fernandez-Rubio, Ester Blanco, Ana Bocanegra, Miriam Echaide, Ibone Labiano, Ana Elsa Huerta, Maria Alsina, Ruth Vera, David Escors, Grazyna Kochan
Summary: Bispecific antibodies hold promise as a therapy for cancer, demonstrating the ability to simultaneously inhibit multiple proteins involved in cancer progression. In lung cancer treatment, their development has been particularly intense due to extensive knowledge of underlying molecular pathways, especially in oncogene-driven tumors. This review provides an overview of the current landscape of bispecific antibodies in lung cancer treatment and discusses potential future expansion of their role.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Inigo Les, Mireia Martinez, Ines Perez-Francisco, Maria Cabero, Lucia Teijeira, Virginia Arrazubi, Nuria Torrego, Ana Campillo-Calatayud, Inaki Elejalde, Grazyna Kochan, David Escors
Summary: Immune-checkpoint inhibitors (ICIs) are widely used in cancer treatment, but they can cause immune-related adverse events (irAEs) in a significant number of patients. Predicting irAEs has become important for managing patients on ICIs. This review discusses biomarkers that have shown potential for predicting irAEs, including those already available for clinical use and those under investigation. Although these biomarkers have not been validated in prospective studies, there is growing evidence supporting their use for predicting and characterizing irAEs, which depend on factors such as the type of cancer, ICI agent, and affected organ. Further research is needed to understand the mechanisms of irAEs and to assess the predictive capacity of different biomarkers.
Article
Biochemistry & Molecular Biology
Ana Bocanegra, Gonzalo Fernandez-Hinojal, Daniel Ajona, Ester Blanco, Miren Zuazo, Maider Garnica, Luisa Chocarro, Elvira Alfaro-Arnedo, Sergio Pineiro-Hermida, Pilar Morente, Leticia Fernandez, Ana Remirez, Miriam Echaide, Maite Martinez-Aguillo, Idoia Morilla, Beatriz Tavira, Alejandra Roncero, Carolina Gotera, Alfonso Ventura, Nerea Recalde, Jose G. Pichel, Juan Jose Lasarte, Luis Montuenga, Ruth Vera, Ruben Pio, David Escors, Grazyna Kochan
Summary: Recent studies show that baseline functional immunity is crucial for the success of immune checkpoint blockade therapies. In this study, high-dimensional systemic immune profiling was performed on non-small-cell lung cancer patients undergoing PD-L1/PD-1 blockade immunotherapy. Responders had a higher diversity of myeloid phenotypes in their peripheral blood. A diversity index was defined as a potential biomarker of response. Fractalkine (FKN), a chemokine linked to immune chemotaxis and adhesion, was identified as a biomarker of response and correlated with myeloid cell diversity. FKN inhibited lung adenocarcinoma growth in both human and mouse models through the involvement of systemic effector NK cells and increased tumor immune infiltration. FKN also sensitized mouse lung cancer models resistant to anti-PD-1 treatment to immunotherapy, indicating its potential therapeutic use in combination with immunotherapy.
Article
Endocrinology & Metabolism
Marta Redondo-Munoz, Francisco Javier Rodriguez-Baena, Paula Aldaz, Adria Caballe-Mestres, Veronica Moncho-Amor, Maddalen Otaegi-Ugartemendia, Estefania Carrasco-Garcia, Ana Olias-Arjona, Irene Lasheras-Otero, Eva Santamaria, Ana Bocanegra, Luisa Chocarro, Abby Grier, M. Monika Dzieciatkowska, Claudia Bigas, Josefina Martin, Uxue Urdiroz-Urricelqui, Florencio Marzo, Enrique Santamaria, Grazyna Kochan, David Escors, Ignacio Marcos Larrayoz, Holger Heyn, Angelo D'Alessandro, Camille Stephan-Otto Attolini, Ander Matheu, Claudia Wellbrock, Salvador Aznar Benitah, Berta Sanchez-Laorden, Imanol Arozarena
Summary: In this study, the anti-anginal drug ranolazine is found to sensitize BRAF inhibitor-resistant melanoma to targeted therapy and immunotherapy by rewiring fatty acid oxidation and the methionine salvage pathway. Resistance of melanoma to targeted therapy and immunotherapy is linked to metabolic rewiring.
Meeting Abstract
Biotechnology & Applied Microbiology
E. Blanco, N. Silva, L. Chocarro, H. Arasanz, A. Bocanegra, L. Fernandez, K. Ausin, J. Fernandez, E. Santamaria, M. Garnica, S. Pineiro, M. Echaide, P. Ramos, R. Vera, D. Escors, C. Smerdou, G. Kochan
HUMAN GENE THERAPY
(2022)
Review
Physics, Multidisciplinary
David Escors, Grazyna Kochan
Summary: Quantum gravity theories require a minimal measurable length, which contradicts the classical uncertainty principle and Lorentz invariance. The generalized uncertainty principle (GUP) from string theories and its modifications have been developed to address these incompatibilities. This has implications for space-time quantization.
Meeting Abstract
Oncology
L. Chocarro, E. Blanco, H. Arasanz, L. Fernandez-Rubio, A. I. Bocanegra, M. Echaide, M. Garnica, P. Ramos, S. Pineiro-Hermida, M. J. Garcia-Granda, R. Vera, E. Santamaria, J. Fernandez-Irigoyen, G. Kochan, D. Escors
ANNALS OF ONCOLOGY
(2022)