Review
Biochemistry & Molecular Biology
FengXia Gao, SiRong He, AiShun Jin
Summary: lncRNAs and miRNAs play significant roles in NK cell biology and diseases, serving as potential biomarkers/targets for early diagnosis, targeted treatment, and prognostic evaluations of NKTL.
Article
Immunology
Xing Tong, Yuhua Ru, Jianhong Fu, Ying Wang, Jinjin Zhu, Yiyang Ding, Fulian Lv, Menglu Yang, Xiya Wei, Chenchen Liu, Xin Liu, Lei Lei, Xiaojin Wu, Lingchuan Guo, Yang Xu, Jie Li, Peng Wu, Huanle Gong, Jia Chen, Depei Wu
Summary: This study suggests that ex vivo fucosylation of NK cells enhances their effector functions in tumor immunotherapy. Fucosylation increases the cytolytic effect of NK cells against B cell lymphoma and promotes their accumulation in targeted tissues. Additionally, fucosylation also enhances T cell anti-tumor immune responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Takayuki Morimoto, Tsutomu Nakazawa, Ryosuke Maeoka, Ichiro Nakagawa, Takahiro Tsujimura, Ryosuke Matsuda
Summary: Glioblastoma (GBM) is an aggressive and malignant brain tumor with poor prognosis. Various treatment strategies have been explored, including immunotherapies. However, current immunotherapies mainly based on T cells have not achieved satisfactory outcomes. This review focuses on the potential of NK cell-based immunotherapy as a novel treatment strategy for GBM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Shuhang Wang, Kun Chen, Yale Jiang, Guo Zhao, Caie Wang, Hong Fang, Qiyu Tang, Chao Sun, Liang Zhang, Haiyang Wu, Li-Feng Zhang, Ning Li
Summary: Natural killer (NK) cell therapy is emerging as a promising cancer treatment that utilizes innate cytotoxic lymphocytes with germline-encoded receptors to kill cancer cells, virus-infected cells, and other stressed cells. NK cells have the advantage of being safe for allogeneic applications and can be used as off-the-shelf cells, overcoming the limitations of autologous cell therapy. However, NK cells have a shorter in vivo persistence compared to T cells, but they have a reservoir of innate immune receptors and can utilize antibody guidance for target recognition.
DRUG DISCOVERY TODAY
(2023)
Article
Oncology
Xavier Chauchet, Laura Cons, Laurence Chatel, Bruno Daubeuf, Gerard Didelot, Valery Moine, Didier Chollet, Pauline Malinge, Guillemette Pontini, Krzysztof Masternak, Walter Ferlin, Vanessa Buatois, Limin Shang
Summary: This study provides detailed mechanisms of how the CD47xCD19 bispecific antibody NI-1701 controls tumor growth in a lymphoma mouse model, including transforming the tumor microenvironment, enhancing immune effector cell responses, and facilitating dendritic cell-mediated phagocytosis. These findings suggest the potential therapeutic value of NI-1701 in the treatment of B-cell lymphoma.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Review
Immunology
Massimo Fantini, Philip Martin Arlen, Kwong Yok Tsang
Summary: Natural killer (NK) cells are important components of the innate immune system that can recognize and suppress the proliferation of cancer cells. Strategies such as boosting NK cells with modulatory cytokines, adoptive NK cell therapy, and the combination of engineered NK cells with monoclonal antibodies (mAbs) that mediate antibody-dependent cell-mediated cytotoxicity (ADCC) have been developed to enhance the antitumor activity of NK cells. The combination of engineered NK cells with mAbs with higher affinity for CD16 expressed on NK cells shows promise in providing more effective and higher-quality treatments for cancer patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Dhanashree Murugan, Vasanth Murugesan, Balaji Panchapakesan, Loganathan Rangasamy
Summary: This paper reviews the role of natural killer (NK) cells in killing tumor cells and the receptors that can be targeted for signaling. It also highlights the potential of nanoparticles in activating NK cells and enhancing their cytotoxic activity against cancer.
Article
Immunology
Zuzana Antosova, Nada Podzimkova, Jakub Tomala, Katerina Augustynkova, Katerina Sajnerova, Eva Nedvedova, Milada Sirova, Guy de Martynoff, David Bechard, Ulrich Moebius, Marek Kovar, Radek Spisek, Irena Adkins
Summary: SOT101, a potential clinical candidate for cancer treatment, activates NK cells and CD8(+) T cells and enhances their cytotoxicity against tumor cells. When used in combination with approved monoclonal antibodies, it increases the killing of tumor cells. In an animal model, the combination of SOT101 and Daratumumab showed the strongest anti-tumor effect, supporting further investigation of this combination in clinical studies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Loredana Cifaldi, Ombretta Melaiu, Roberto Giovannoni, Monica Benvenuto, Chiara Focaccetti, Daniela Nardozi, Giovanni Barillari, Roberto Bei
Summary: DNAM-1 is a crucial NK cell activating receptor that contributes significantly to the killing of tumor or virus-infected cells by binding to specific ligands, alongside NKG2D and NCRs. DNAM-1 specifically recognizes PVR and Nectin-2 ligands expressed on a wide range of tumor cells and virus-infected cells. Although NK cells engineered with different antigen chimeric receptors or chimeric NKG2D receptors have been extensively studied, the use of DNAM-1 chimeric receptor-engineered NK cells has only been proposed in a recent proof-of-concept study. This perspective study aims to explain the rationale behind using this novel tool as a new anti-cancer immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Sizhe Liu, Vasiliy Galat, Yekaterina Galat, Yoo Kyung Annie Lee, Derek Wainwright, Jennifer Wu
Summary: NK cells, as a specialized immune effector cell type, play a critical role in immune activation against abnormal cells. Unlike T cell activation, NK cell activation is governed by interactions between NK receptors and target cells, leading to significant attention in cancer immunotherapy. Many efforts are focused on developing and engineering NK cell-based cancer immunotherapy.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Engineering, Biomedical
Shuojiong Pan, Tianyu Li, Yizheng Tan, Huaping Xu
Summary: In this study, selenium-containing nanoparticles were constructed to synergistically enhance Pem-based chemotherapy and NK cell-based immunotherapy. The selenium compounds could deliver Pem to tumor sites and improve the chemotherapy efficiency. Additionally, they can also activate NK cell's immune response. The in vitro and in vivo experiments revealed the potential mechanism, highlighting the promising prospect of this strategy in chemoimmunotherapy.
Review
Immunology
Barbara Seliger, Ulrike Koehl
Summary: This article provides an overview of NK cell biology, the impact of tumor cells and the tumor microenvironment on NK cells, and the latest advancements in NK cell-based therapeutic strategies. The article emphasizes the challenges of tumor cells evading NK cell recognition and NK cell immune suppression, and highlights the need to explore and improve treatment strategies.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Nina Miazek-Zapala, Aleksander Slusarczyk, Aleksandra Kusowska, Piotr Zapala, Matylda Kubacz, Magdalena Winiarska, Malgorzata Bobrowicz
Summary: Despite the availability of treatments that can cure hematological malignancies, their implementation is limited by patient age and frailty, and they often come with undesirable side effects. Therefore, cell-based immunotherapy may be the optimal strategy to be successfully incorporated into standard treatment protocols in the future.
Article
Immunology
Kai Zhang, Enwu Yuan
Summary: This study created a unique prognostic profile based on NK cell marker genes that can accurately predict the efficacy of immunotherapy for HCC patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Wu Yi, Tianxin Yang, Sisi Lin, Rui Hao, Jin Yu, Ying Wang, Xiangming Tong
Summary: Extranodal NK/T cell lymphoma is a rare subtype of lymphoma with poor prognosis. It commonly occurs in the nasal cavity, nasopharynx, paranasal sinuses, tonsils, and larynx. The resistance of ENKL cells to anthracycline-based chemotherapy is due to P-glycoprotein expression. New treatments such as immune checkpoint inhibitors, histone deacetylase inhibitors, and monoclonal antibodies are being investigated.
CANCER MANAGEMENT AND RESEARCH
(2022)
Review
Biotechnology & Applied Microbiology
Christian Klein, Candice Jamois, Tina Nielsen
Summary: The introduction of anti-CD20 monoclonal antibody therapy with rituximab in the 1990s significantly improved outcomes for patients with B-cell malignancies. Novel anti-CD20 antibodies like atumumab, ublituximab, and obinutuzumab have been developed with structural and mechanistic differences from rituximab, showing improved efficacy in clinical trials.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2021)
Article
Oncology
Mohamed-Reda Benmebarek, Bruno L. Cadilha, Monika Herrmann, Stefanie Lesch, Saskia Schmitt, Stefan Stoiber, Abbass Darwich, Christian Augsberger, Bettina Brauchle, Lisa Rohrbacher, Arman Oner, Matthias Seifert, Melanie Schwerdtfeger, Adrian Gottschlich, Felicitas Rataj, Nadja C. Fenn, Christian Klein, Marion Subklewe, Stefan Endres, Karl-Peter Hopfner, Sebastian Kobold
Summary: A modular and controllable MHC-unrestricted adoptive T cell therapy platform tailored to AML has been developed, combining synthetic agonistic receptor (SAR) -transduced T cells with AML-targeting tandem single chain variable fragment (scFv) constructs. This platform shows selective killing of AML cells and persistent responses in xenograft models, indicating its potential for further translation in AML treatment.
Article
Oncology
Zhaoming Wang, Michael S. Chimenti, Christopher Strouse, George J. Weiner
Summary: The study found that T cell help, mainly mediated by local production of IL2, plays a significant role in enhancing NK cell-mediated antibody-dependent cellular cytotoxicity and viability. Activating T cells can improve the efficacy of anti-CD20 and other mAb therapies, particularly when NK-mediated antibody-dependent cellular cytotoxicity is the primary mechanism of action.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Immunology
Vittoria Massafra, Sofia Tundo, Aline Dietzig, Axel Ducret, Christian Jost, Christian Klein, Roland E. Kontermann, Hendrik Knoetgen, Martin Steegmaier, Andrea Romagnani, Yvonne A. Nagel
Summary: This study explores the potential of targeted protein degradation in tumor cells to enhance T cell effector function, and for the first time investigates the impact of combining a degrader and a TCB in cancer immunotherapy.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Biology
S. Jordan Kerns, Chaitra Belgur, Debora Petropolis, Marianne Kanellias, Riccardo Barrile, Johannes Sam, Tina Weinzierl, Tanja Fauti, Anne Freimoser-Grundschober, Jan Eckmann, Carina Hage, Martina Geiger, Patrick Ray Ng, William Tien-Street, Dimitris Manatakis, Virginie Micallef, Regine Gerard, Michael Bscheider, Ekaterina Breous-Nystrom, Anneliese Schneider, Anna Maria Giusti, Cristina Bertinetti-Lapatki, Heather Shannon Grant, Adrian B. Roth, Geraldine A. Hamilton, Thomas Singer, Katia Karalis, Annie Moisan, Peter Bruenker, Christian Klein, Marina Bacac, Nikolce Gjorevski, Lauriane Cabon
Summary: This study demonstrated the unprecedented capability of two human Organs-on-Chips in evaluating the safety profile of T-cell bispecific antibodies targeting tumor antigens, predicting TCB safety liabilities based on target expression and antibody affinity. These novel tools broaden research options for understanding engineered therapeutic antibodies and assessing safety in tissues susceptible to adverse events.
Article
Oncology
Gabrielle Leclercq, Helene Haegel, Anneliese Schneider, Anna Maria Giusti, Estelle Marrer-Berger, Christophe Boetsch, Antje-Christine Walz, Vesna Pulko, Johannes Sam, John Challier, Cristiano Ferlini, Alex Odermatt, Pablo Umana, Marina Bacac, Christian Klein
Summary: The study demonstrates that dasatinib can effectively serve as a pharmacological on/off switch to mitigate off-tumor toxicities or CRS induced by T cell bispecific antibodies. By providing pharmacologically relevant doses, dasatinib can regulate T cell activation, cell killing, and cytokine release triggered by T cell engagers.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Raquel Delgado, Karoline Kielbassa, Johanna ter Burg, Christian Klein, Christine Trumpfheller, Koen de Heer, Arnon P. Kater, Eric Eldering
Summary: The study revealed that selicrelumab can enhance the sensitivity of CLL cells to CD20 monoclonal antibodies, despite its minimal pro-survival effect. Combining selicrelumab with anti-CD20 antibodies may be a promising therapeutic strategy for CLL.
Article
Hematology
Jonathan C. Strefford, Malgorzata Nowicka, Chantal E. Hargreaves, Cathy Burton, Andrew Davies, Rosalind Ganderton, Wolfgang Hiddemann, Chisako Iriyama, Wolfram Klapper, Kate Latham, Maurizio Martelli, Farheen Mir, Helen Parker, Kathleen N. Potter, Matthew J. J. Rose-Zerilli, Laurie H. Sehn, Marek Trneny, Umberto Vitolo, Christopher R. Bolen, Christian Klein, Andrea Knapp, Mikkel Z. Oestergaard, Mark S. Cragg
Summary: This study demonstrates that Fc gamma R genotype is not associated with response to rituximab/obinutuzumab plus chemotherapy in treatment-naive patients with advanced FL or DLBCL.
Article
Biochemistry & Molecular Biology
Steffen Dickopf, Can Buldun, Vedran Vasic, Guy Georges, Carina Hage, Klaus Mayer, Matthias Forster, Uwe Wessels, Kay-Gunnar Stubenrauch, Jorg Benz, Andreas Ehler, Matthias E. Lauer, Philippe Ringler, Sebastian Kobold, Stefan Endres, Christian Klein, Ulrich Brinkmann
Summary: The field of multi-specific antibody derivatives is rapidly growing, with domain exchange reactions being able to generate hybrid antibodies under physiological conditions for potential therapeutic applications.
BIOLOGICAL CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Alvaro Teijeira, Itziar Migueliz, Saray Garasa, Vaios Karanikas, Carlos Luri, Asunta Cirella, Irene Olivera, Marta Canamero, Maite Alvarez, Maria C. Ochoa, Ana Rouzaut, Maria E. Rodriguez-Ruiz, Miguel F. Sanmamed, Christian Klein, Pablo Umana, Mariano Ponz, Marina Bacac, Ignacio Melero
Summary: In this study, the performance of the CEA-CD3 T cell bispecific antibody cibisatamab in three-dimensional tumor organoids cocultured with T cells was investigated using time-lapse confocal microscopy. The results showed that the killing of tumor cells was dependent on the levels of surface CEA expression, and the higher affinity CEACAM5-CD3 bispecific antibody remained active on low CEA expressing organoids. Additionally, the coculture of tumor organoids, autologous fibroblasts, and T cells demonstrated a costimulatory effect of anti-FAP-4-1BBL antibody, leading to enhanced tumor cell killing.
Article
Oncology
Gabrielle Leclercq, Llucia Alberti Servera, Sabrina Danilin, John Challier, Nathalie Steinhoff, Claudia Bossen, Alex Odermatt, Valeria Nicolini, Pablo Umana, Christian Klein, Marina Bacac, Anna-Maria Giusti, Anneliese Schneider, Helene Haegel
Summary: This study investigated the biological mechanisms of cytokine release after treatment with T cell bispecific antibodies (TCBs) and identified T cells as the triggers and monocytes and neutrophils as the amplifiers of the cytokine cascade. Moreover, it demonstrated the contribution of neutrophils to TCB-mediated cytokine release using single-cell RNA sequencing.
Article
Oncology
Gabrielle Leclercq, Helene Haegel, Alberto Toso, Tina Zimmermann, Luke Green, Nathalie Steinhoff, Johannes Sam, Vesna Pulko, Anneliese Schneider, Anna Maria Giusti, John Challier, Anne Freimoser-Grundschober, Laurent Lariviere, Alex Odermatt, Martin Stern, Pablo Umana, Marina Bacac, Christian Klein
Summary: This study aimed to identify small molecules that can reduce cytokine release while maintaining T cell-mediated tumor killing. By screening a library of FDA-approved kinase inhibitors, mTOR, JAK, and Src kinase inhibitors were found to modulate cytokine release. Further in vitro and in vivo experiments confirmed these findings and supported the evaluation of these inhibitors as a treatment to prevent cytokine release syndrome (CRS).
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Oncology
Gabrielle Leclercq, Nathalie Steinhoff, Helene Haegel, Donata De Marco, Marina Bacac, Christian Klein
Summary: T cell engaging therapies redirect T cells towards tumor cells, leading to cytotoxicity. However, this can trigger a release of pro-inflammatory cytokines causing Cytokine Release Syndrome (CRS), which remains a major safety concern. Mitigation strategies are necessary to reduce cytokine release while maintaining efficacy. Tyrosine kinase inhibitors are emerging as a potential strategy for managing CRS symptoms.
Review
Oncology
Andrew Davies, Arnon P. Kater, Jeff P. Sharman, Stephan Stilgenbauer, Umberto Vitolo, Christian Klein, Joana Parreira, Gilles Salles
Summary: The type II anti-CD20 antibody obinutuzumab has shown improved efficacy compared to rituximab in the treatment of indolent non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL). Ongoing research is focusing on biomarkers and developing chemotherapy-free regimens involving obinutuzumab.
Article
Cell Biology
Ester Fagnano, Swati Pendharkar, Madyson Colton, Philip N. Jones, Marta Crespi Sallan, Tetyana Klymenko, Andrejs Braun, Christian Klein, Jamie Honeychurch, Eleanor J. Cheadle, Timothy M. Illidge
Summary: This study showed that contact between tumor cells and stromal cells inhibits the effector functions of Obinutuzumab, highlighting the potential for improved therapies targeting the microenvironment to enhance patient outcomes in B-cell malignancies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
