Article
Immunology
Julia Harwardt, Stefania C. Carrara, Jan P. Bogen, Katrin Schoenfeld, Julius Grzeschik, Bjoern Hock, Harald Kolmar
Summary: The construction of trispecific IgG-like antibodies is a challenging task due to the need for combining at least three different binding moieties. This study presents the construction of trispecific natural killer cell engagers using a two-in-one antibody combined with a novel anti-CD16a common light chain module identified through yeast surface display screening. The resulting antibodies target epidermal growth factor receptor (EGFR), programmed death-ligand 1 (PD-L1), and CD16a simultaneously, showing specific cellular binding properties and a strong ADCC effect. This research opens up possibilities for developing multispecific therapeutic antibodies with desired target combinations, valencies, molecular symmetries, and architectures through avian immunization.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Jan P. Bogen, Stefania C. Carrara, David Fiebig, Julius Grzeschik, Bjoern Hock, Harald Kolmar
Summary: In this study, chicken-derived antibodies targeting EGFR were affinity matured and used to isolate CD16a- and PD-L1-specific monoclonal antibodies. Humanized bispecific and trispecific variants were generated, showing elevated ADCC and synergistic effects of trispecific antigen binding. This work paves the way for the engineering of tri- and oligospecific therapeutic antibodies derived from avian immunizations.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Hui-yang Wu, Ke-xin Li, Wan-ying Pan, Meng-qi Guo, Dei-zhi Qiu, Yan-jie He, Yu-hua Li, Yu-xian Huang
Summary: The combination of Venetoclax and NK cells demonstrates a synergistic cytolysis effect on AML cells by activating the NKG2D/NKG2DL ligand-receptor pathway and involving the NFKB signaling pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Anne-Sophie Chretien, Raynier Devillier, Samuel Granjeaud, Charlotte Cordier, Clemence Demerle, Nassim Salem, Julia Wlosik, Florence Orlanducci, Laurent Gorvel, Stephane Fattori, Marie-Anne Hospital, Jihane Pakradouni, Emilie Gregori, Magali Paul, Philippe Rochigneux, Thomas Pagliardini, Mathieu Morey, Cyril Fauriat, Nicolas Dulphy, Antoine Toubert, Herve Luche, Marie Malissen, Didier Blaise, Jacques A. Nunes, Norbert Vey, Daniel Olive
Summary: The accumulation of CD56(-)CD16(+) unconventional NK cells in patients with acute myeloid leukemia may be a consequence of immune escape from innate immunity during AML progression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Sarah B. Reusing, Dan A. Vallera, Angela R. Manser, Titus Vatrin, Sanil Bhatia, Martin Felices, Jeffrey S. Miller, Markus Uhrberg, Florian Babor
Summary: The text discusses the complexity and rarity of biphenotypic acute lymphoblastic leukemia in children, characterized by CD33 expression. Despite therapies targeting CD19, relapse and resistance remain challenges. Testing the BiKE on NK cells from healthy volunteers and leukemia patients showed enhanced effector functions against CD33(+) cells, suggesting potential as a therapeutic option.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Cell Biology
Antonio Arulanandam, Liang Lin, Hao-Ming Chang, Martine Cerutti, Sylvie Choblet, Peng Gao, Armin Rath, Armand Bensussan, Jean Kadouche, Daniel Teper, Ofer Mandelboim, Wei Li
Summary: GPC3 is highly expressed in multiple solid tumors and is barely expressed in adult normal tissues except the placenta. NKp46 activation receptor is expressed in all-natural killer cells, including tumor-infiltrating NK cells. CYT-303 is a multifunctional antibody that targets both GPC3 and NKp46 to mediate NK cell-redirected killing of HCC tumors.
Article
Immunology
Raffaella Meazza, Loredana Ruggeri, Fabio Guolo, Paola Minetto, Paolo Canevali, Fabrizio Loiacono, Sara Ciardelli, Alessandra Bo, Silvia Luchetti, Alberto Serio, Letizia Zannoni, Christelle Retiere, Natalia Colomar-Carando, Sarah Parisi, Antonio Curti, Roberto M. M. Lemoli, Daniela Pende
Summary: NK cell-based adoptive immunotherapy in leukemia patients has shown efficacy and safety. This study compared two approaches to determine the size of alloreactive NK cells in HLA-haploidentical donors for AML patients. The phenotypic identification of NK cells and degranulation assays proved to be accurate and efficient methods for determining the size of alloreactive NK cell subset.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Malena Bodden, Aline Haecker, Jasmin Roeder, Anne Kiefer, Congcong Zhang, Anita Bhatti, Jordi Pfeifer Serrahima, Evelyn Ullrich, Ines Kuehnel, Winfried S. Wels
Summary: In contrast to T lymphocytes, natural killer (NK) cells do not require prior sensitization but are rapidly activated upon encountering virally infected or neoplastic cells. In addition, NK cells can be safely applied in an allogeneic setting, making them important effector cells for the development of off-the-shelf therapeutics for adoptive cancer immunotherapy.
Article
Biochemistry & Molecular Biology
Jesper van Eck van der Sluijs, Diede van Ens, Jolanda Brummelman, Daan Heister, Aastha Sareen, Lisa Truijen, Dorette S. van Ingen Schenau, Mirjam H. M. Heemskerk, Marieke Griffioen, Michel G. D. Kester, Nicolaas P. M. Schaap, Joop H. Jansen, Anniek B. van der Waart, Harry Dolstra, Willemijn Hobo
Summary: Non-DCs have been found to enhance the activation and expansion of antigen-specific CD8+ T cells mediated by DCs, without impairing the NK cell responses in vitro and in vivo. This provides a rationale for further clinical translation of the CD34+-derived DC-complete vaccine in hemato-oncology patients post alloSCT.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Seong Guk Park, Heeyeon Kim, Heejin Jun, Sun Young Choi, Eunhee Kim, Sebyung Kang
Summary: The combination of affibody molecules, cytotoxic RTA, and intracellularly designating KDEL signal peptide successfully developed cancer-specific and efficacious ricin-based RITs. The in vivo efficacy of RITs was enhanced by introducing the albumin binding domain, effectively suppressing tumor growth without noticeable side-effects. This approach can be applied to develop novel protein-based magic bullets to effectively suppress tumors resistant to conventional anti-cancer drugs.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Cell Biology
Darren Chen Pei Wong, E. Hui Clarissa Lee, Junzhi Er, Ivan Yow, Ricky Abdi Gunawan Koean, Owen Ang, Jingwei Xiao, Boon Chuan Low, Jeak Ling Ding
Summary: We demonstrated that NK cell transcription factor Eomes undergoes nuclear shuttling and enhances NK cell contractility during lung cancer cell surveillance. NK cells respond to TGF-beta in the coculture medium to sustain intracellular contractility and promote Eomes nuclear localization. This mechanism increases NK cell cytotoxicity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Immunology
Tae-Shin Kim, Min-Seok Rha, Eui-Cheol Shin
Summary: IL-15 plays a pleiotropic role in NK and CD8(+) T cells and contributes to host protection or immunopathology during infection. This study shows that IFN-gamma more effectively upregulates IL-15 expression in Huh-7 cells compared to IFN-alpha and IFN-beta. IRF1 and Kappa B kinase alpha/beta are involved in the upregulation of IL-15. Additionally, IL-15 on IFN-gamma-treated Huh-7 cells activates NK cells through trans-presentation.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Prayag J. Amin, Bhavani S. Shankar
Summary: This study assessed the effect of Tinospora cordifolia polysaccharide G1-4A on natural killer (NK) cells. It was found that G1-4A can directly activate NK cells and also activate them through interactions with dendritic cells (DC). This research suggests that G1-4A has the potential to be used as an immunotherapeutic agent.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2023)
Article
Oncology
Irene Veneziani, Paola Infante, Elisa Ferretti, Ombretta Melaiu, Cecilia Battistelli, Valeria Lucarini, Mirco Compagnone, Carmine Nicoletti, Aurora Castellano, Stefania Petrini, Marzia Ognibene, Annalisa Pezzolo, Lucia Di Marcotullio, Roberto Bei, Lorenzo Moretta, Vito Pistoia, Doriana Fruci, Vincenzo Barnaba, Franco Locatelli, Loredana Cifaldi
Summary: The study demonstrated that Nutlin-3a could enhance NK cell-mediated killing of neuroblastoma cells by restoring p53 function and increasing ligand expression for NK-ARs. Adoptive transfer of human NK cells into neuroblastoma-bearing mice resulted in tumor shrinkage and improved overall survival. Nutlin-3a also boosted NK cell-mediated cytotoxicity against neuroblastoma spheroids by increasing ligand expression in primary neuroblastoma cells.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Materials Science, Biomaterials
Nikita Subedi, Liesbeth Petronella Verhagen, Paul de Jonge, Laura C. Van Eyndhoven, Mark C. van Turnhout, Vera Koomen, Jean Baudry, Klaus Eyer, Harry Dolstra, Jurjen Tel
Summary: Increasing evidence suggests that natural killer (NK) cells, composed of distinct functional subsets, have potential for anticancer immunotherapy. Single-cell analysis using microfluidics reveals variable response of NK cells to different target cells. CD34+ hematopoietic progenitor (HPC)-NK cells derived from umbilical cord blood display superior antitumor cytotoxicity. Interaction with target cells enhances cytotoxicity and cytokine secretion of NK cells.
Article
Biophysics
Christoph Schmid, Myriam Labopin, Nicolaas Schaap, Hendrik Veelken, Arne Brecht, Michael Stadler, Juergen Finke, Frederic Baron, Matthew Collin, Gesine Bug, Per Ljungman, Didier Blaise, Johanna Tischer, Adrian Bloor, Aleksander Kulagin, Sebastian Giebel, Norbert-Claude Gorin, Jordi Esteve, Fabio Ciceri, Bipin Savani, Arnon Nagler, Mohamad Mohty
Summary: This study analyzed 318 acute leukemia patients who received DLI after alloSCT, showing that preemptive DLI was effective in reducing MRD and increasing chimerism, thus improving survival rates for patients.
BONE MARROW TRANSPLANTATION
(2022)
Article
Biochemical Research Methods
Erik H. L. P. G. Huys, Willemijn Hobo, Frank W. M. B. Preijers
Summary: The 10-color panel with 21 monoclonal antibodies is designed for fast and comprehensive screening of leukemia and lymphoma cells in all hematopoietic cell lineages. By stacking conjugates in one color due to limited PMTs, it enables simultaneous analysis of aberrant cells and improves the diagnostic potential for hematological malignancies.
Article
Medical Laboratory Technology
Vincent H. J. van der Velden, Frank Preijers, Ulrika Johansson, Theresia M. Westers, Alan Dunlop, Anna Porwit, Marie C. Bene, Peter Valent, Jeroen te Marvelde, Orianne Wagner-Ballon, Uta Oelschlaegel, Leonie Saft, Sharham Kordasti, Robin Ireland, Eline Cremers, Canan Alhan, Carolien Duetz, Willemijn Hobo, Nicolas Chapuis, Michaela Fontenay, Peter Bettelheim, Lisa Eidenshink-Brodersen, Patricia Font, Michael R. Loken, Sergio Matarraz, Kiyoyuki Ogata, Alberto Orfao, Katherina Psarra, Dolores Subira, Denise A. Wells, Matteo G. Della Porta, Kate Burbury, Frauke Bellos, Elisabeth Weiss, Wolfgang Kern, Arjan van de Loosdrecht
Summary: This article reviews the progress of flow cytometry (FCM) in the diagnosis of myelodysplastic syndrome (MDS) in recent years, and provides optimal methods and recommendations for sample processing, antibody panels and fluorochromes, and current hardware technologies. These recommendations will facilitate the appropriate application of FCM assays in the diagnostic workup of MDS patients, but further standardization and harmonization are needed.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2023)
Article
Medical Laboratory Technology
Arjan A. Loosdrecht, Wolfgang Kern, Anna Porwit, Peter Valent, Sharham Kordasti, Eline Cremers, Canan Alhan, Carolien Duetz, Alan Dunlop, Willemijn Hobo, Frank Preijers, Orianne Wagner-Ballon, Nicolas Chapuis, Michaela Fontenay, Peter Bettelheim, Lisa Eidenschink-Brodersen, Patricia Font, Ulrika Johansson, Michael R. Loken, Jeroen G. Marvelde, Sergio Matarraz, Kiyoyuki Ogata, Uta Oelschlaegel, Alberto Orfao, Katherina Psarra, Dolores Subira, Denise A. Wells, Marie C. Bene, Matteo G. Della Porta, Kate Burbury, Frauke Bellos, Vincent H. J. van der Velden, Theresia M. Westers, Leonie Saft, Robin Ireland
Summary: This article discusses the rationale for including flow cytometry (FCM) in the diagnostic investigation and evaluation of cytopenias and suspected myelodysplastic syndromes (MDS) by the European LeukemiaNet international MDS Flow Working Group. The WHO 2016 classification acknowledges the contribution of FCM in the diagnosis of MDS and its potential usefulness in prognostication, prediction, therapy evaluation, and patient follow-up.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2023)
Article
Immunology
Maarten Versteven, Donovan Flumens, Diana Campillo-Davo, Hans De Reu, Laura Van Bruggen, Stefanie Peeters, Viggo Van Tendeloo, Zwi Berneman, Harry Dolstra, Sebastien Anguille, Willemijn Hobo, Evelien Smits, Eva Lion
Summary: Dendritic cell (DC) vaccines have shown promise in cancer immune therapy, but further optimization is needed to improve their clinical responses. Silencing PD-L1 and PD-L2 can enhance the stimulatory potential of DC vaccines and improve the efficacy of anti-tumor immunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Claire N. Harrison, Nicolaas Schaap, Alessandro M. Vannucchi, Jean-Jacques Kiladjian, Francesco Passamonti, Sonja Zweegman, Moshe Talpaz, Srdan Verstovsek, Shelonitda Rose, Jun Zhang, Oumar Sy, Ruben A. Mesa
Summary: This study evaluated the efficacy and safety of Fedratinib in patients with low baseline platelet counts. The results indicated that Fedratinib 400 mg/day is safe and effective for patients with low platelet counts, and no initial dose adjustment is required.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Pathology
Leonie Kroeze, B. Scheijen, K. M. Hebeda, J. Rijntjes, J. A. C. W. Luijks, D. Evers, W. Hobo, P. J. T. A. Groenen, M. van den Brand
Summary: Clonality assessment by detecting immunoglobulin gene rearrangements is important for determining the clonal relationship between concurrent or subsequent lymphoid malignancies. This study used next generation sequencing to analyze clonality and mutation in a patient diagnosed with B-cell acute lymphoblastic leukemia followed by histiocytic sarcoma. The results showed the evolution of multiple subclones, with one subclone acquiring a RAF1 mutation and evolving into histiocytic sarcoma.
Article
Multidisciplinary Sciences
Katrin Rabold, Martijn Zoodsma, Inge Grondman, Yunus Kuijpers, Manita Bremmers, Martin Jaeger, Bowen Zhang, Willemijn Hobo, Han J. Bonenkamp, Johannes H. W. de Wilt, Marcel J. R. Janssen, Lenneke A. M. Cornelissen, Ilse C. H. Van Engen-van Grunsven, Willem J. M. Mulder, Jan W. A. Smit, Gosse J. Adema, Mihai G. Netea, Yang Li, Cheng-Jian Xu, Romana T. Netea-Maier
Summary: This study conducted single-cell transcriptomics and functional analyses of myeloid cells in patients with non-medullary thyroid carcinoma and multinodular goiter, revealing distinct transcriptional and functional changes occurring in these cells before their tumor infiltration, which are already initiated in the bone marrow.
NATURE COMMUNICATIONS
(2022)
Review
Medical Laboratory Technology
Anna Porwit, Marie C. Bene, Carolien Duetz, Sergio Matarraz, Uta Oelschlaegel, Theresia M. Westers, Orianne Wagner-Ballon, Shahram Kordasti, Peter Valent, Frank Preijers, Canan Alhan, Frauke Bellos, Peter Bettelheim, Kate Burbury, Nicolas Chapuis, Eline Cremers, Matteo G. Della Porta, Alan Dunlop, Lisa Eidenschink-Brodersen, Patricia Font, Michaela Fontenay, Willemijn Hobo, Robin Ireland, Ulrika Johansson, Michael R. Loken, Kiyoyuki Ogata, Alberto Orfao, Katherina Psarra, Leonie Saft, Dolores Subira, Jeroen te Marvelde, Denise A. Wells, Vincent H. J. van der Velden, Wolfgang Kern, Arjan A. van de Loosdrecht
Summary: Multiparameter flow cytometry (MFC) is an essential method in bone marrow investigation for patients with cytopenia and suspected myelodysplastic syndrome (MDS), providing valuable information for diagnosis and treatment follow-up. This document summarizes recommendations from the ELN iMDS Flow on analytical issues in MFC, including the analysis of different cell subsets and the use of specific markers for MDS diagnosis. Machine-learning-based analytical tools and large uniform datasets are suggested for future research to improve integrated diagnostics and risk stratification in MDS.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2023)
Article
Oncology
Martin Felices, Erin Wesley, Laura E. Bendzick, Behiye Kodal, Rachel Hopps, Bartosz Grzywacz, Peter Hinderlie, Jeffrey S. Miller, Melissa A. Geller
Summary: We investigated the effects of combined treatment with an IL15 superagonist (N-803) and immune checkpoint blockade (ICB) on immune activation in ovarian cancer patients. Our results showed that N-803 stimulated initial expansion of natural killer (NK) cells in patients, and combining ICB enhanced NK cell function. In preclinical studies, the combination of N-803 and ICB also showed improved anti-tumor control and enhanced NK cell persistence and expansion in vivo.
CANCER IMMUNOLOGY RESEARCH
(2023)
Review
Oncology
Jawad Fares, Zachary B. Davis, Julian S. Rechberger, Stephanie A. Toll, Jonathan D. Schwartz, David J. Daniels, Jeffrey S. Miller, Soumen Khatua
Summary: Despite current treatment advancements for brain tumors, including surgery, chemotherapy, and radiation, the prognosis remains poor, especially for recurrent cases. The close proximity to delicate neural structures often prevents complete surgical removal, and the toxicities of systemic therapy are a concern. However, the field of NK cell-based cancer therapy shows promise as a new avenue for treating brain tumors.
NPJ PRECISION ONCOLOGY
(2023)
Article
Hematology
Shernan G. Holtan, Andrea Hoeschen, Qing Cao, Celalettin Ustun, Brian C. Betts, Najla El Jurdi, Joseph Maakaron, Armin Rashidi, Jeffrey S. Miller, John E. Wagner, Bruce R. Blazar, Pamala A. Jacobson, Angela Panoskaltsis-Mortari, Daniel J. Weisdorf, Margaret L. Macmillan
Summary: Studies have shown that treatments that aid inflammation resolution, immune tolerance, and epithelial repair may improve outcomes for life-threatening acute graft-versus-host disease (aGVHD) beyond traditional immunosuppressants. Addition of urinary-derived human chorionic gonadotropin/epidermal growth factor (uhCG/EGF) to standard aGVHD therapy has been found to be a feasible supportive care measure with potential to reduce morbidity and mortality. Further research is needed to explore the efficacy of uhCG/EGF as a complementary treatment for aGVHD.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Meeting Abstract
Biophysics
K. Kirgizov, R. Greco, M. Badoglio, M. Labopin, R. Saccardi, M. Rovira, D. Farge, N. Schaap, J. Moore, A. Polushin, J. Finke, T. Alexander, J. Burman, N. del Papa, D. M. Greenfield, M. Kazmi, A. Rovo, H. Schoemans, B. Sharrack, A. Tichelli, P. Bader, S. Corbacioglu, Z. Peric, G. W. Basak, J. A. Snowden
BONE MARROW TRANSPLANTATION
(2022)
Meeting Abstract
Biophysics
O. Penack, T. Luft, C. Peczynski, A. Benner, P. Ambron, E. Polge, M. Badoglio, S. Sica, M. Arat, M. Itala-Remes, D. Caballero, N. Schaap, M. Karas, L. Raida, T. Schroeder, P. Dreger, E. Metafuni, T. Ozcelik, T. Gooley, B. Sandmaier, L. Kordelas, I. Moiseev, H. Schoemans, C. Koenecke, G. W. Basak, Z. Peric
BONE MARROW TRANSPLANTATION
(2022)
Meeting Abstract
Oncology
A. Reiter, Kiladjian J.-J, A. Tefferi, F. Passamonti, A. Vannucchi, M. Talpaz, F. Cervantes, C. N. Harrison, R. A. Mesa, J. Mascarenhas, N. Schaap, S. Verstovsek, T. Devos, S. Rose, J. Zhang, O. Sy, A. Pardanani
ONCOLOGY RESEARCH AND TREATMENT
(2022)
