Article
Oncology
Congcong Zhang, Jasmin Roeder, Anne Scherer, Malena Bodden, Jordi Pfeifer Serrahima, Anita Bhatti, Anja Waldmann, Nina Mueller, Pranav Oberoi, Winfried S. Wels
Summary: The study developed a bispecific antibody NKAB-ErbB2 that redirects NKG2D-expressing effector cells to ErbB2-positive tumor cells, synergizing with NKG2D-CAR cells and natural NK cell-mediated cytotoxicity. In mouse model, NKAR-NK-92 cells combined with NKAB-ErbB2 effectively suppressed tumor outgrowth and induced antitumor immunity and cures in most animals.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Multidisciplinary Sciences
Jiao Wang, Sandra Toregrosa-Allen, Bennett D. Elzey, Sagar Utturkar, Nadia Atallah Lanman, Victor Bernal-Crespo, Matthew M. Behymer, Gregory T. Knipp, Yeonhee Yun, Michael C. Veronesi, Anthony L. Sinn, Karen E. Pollok, Randy R. Brutkiewicz, Kathryn S. Nevel, Sandro Matosevic
Summary: This study demonstrates a promising strategy utilizing genetically engineered human NK cells as a multifunctional immunotherapy to target multiple mechanisms of GBM progression simultaneously, including addressing antigen escape, immunometabolic reprogramming, and immune cell homing.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Oncology
Francesco Tamiro, Andrew P. Weng, Vincenzo Giambra
Summary: Leukemia-initiating cells (LIC) are unique cells in different types of leukemia that have self-renewing capabilities and produce tumors, which are functionally distinct from bulk leukemia cells. Current conventional treatments are not effective in eliminating LICs, hence innovative therapeutics targeting LICs hold promise for developing an effective cure for ALL.
Review
Oncology
Nobuyoshi Arima
Summary: NK cells were originally thought to be part of the innate immune system playing a protective role against tumors and viral infections. The outcomes of allogeneic hematopoietic stem cell transplantation can provide insights into the antitumor and regulatory effects of NK cells through HLA class 1 matching. New treatment strategies based on these concepts may offer personalized treatment options and increase the possibility of a cure for leukemia patients.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Multidisciplinary Sciences
Amanda A. van Vliet, Ella Peters, Denise Vodegel, Danielle Steenmans, Monica Raimo, Susan Gibbs, Tanja D. de Gruijl, Adil D. Duru, Jan Spanholtz, Anna-Maria Georgoudaki
Summary: UCB CD34(+) progenitor cell-derived NK cells showed efficient cytotoxicity against melanoma cells, and this performance was consistent among different UCB donors and correlated with the levels of IFNg, TNF, perforin and granzyme B. Perforin and granzyme B levels predicted NK cell cytotoxic capacity. The involvement of multiple activating receptors, especially TRAIL, was identified as the mode of action for the synergistic cytotoxic NK cell activity.
Review
Immunology
Siqin Duan, Shuwen Liu
Summary: This review highlights the immunotherapy strategies for HIV infection that utilize the beneficial properties of natural killer (NK) cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Rui Zhang, Qingxi Liu, Sa Zhou, Hongpeng He, Mingfeng Zhao, Wenjian Ma
Summary: In this study, a genetically modified bifunctional CAR-NK cell therapy was developed for the treatment of acute myeloid leukemia (AML). The bifunctional CD33/B16 CAR-NK cells showed superior killing efficiency towards AML cells compared to CAR-NK cells targeting CD33 only. In vivo studies also demonstrated effective clearance of leukemic cells and improved survival. These findings suggest a promising CAR-NK approach for AML treatment and potentially other tumors.
Article
Oncology
Pauline Rettman, Matthew D. Blunt, Rebecca J. Fulton, Andres F. Vallejo, Leidy Y. Bastidas-Legarda, Laura Espana-Serrano, Marta E. Polak, Aymen Al-Shamkhani, Christelle Retiere, Salim Khakoo
Summary: This study demonstrates the feasibility of a peptide-based KIR-targeting vaccine strategy to activate NK cells and enhance antitumor responses. The DNA vaccine upregulated genes associated with cellular metabolism and downregulated genes related to immune cell maturation. Vaccination led to enhanced antitumor responses against melanoma cells and a tumor model expressing the KIR2DS2 ligand HLA-C*0102.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Chia-Ing Jan, Shi-Wei Huang, Peter Canoll, Jeffrey N. Bruce, Yu-Chuan Lin, Chih-Ming Pan, Hsin-Man Lu, Shao-Chih Chiu, Der-Yang Cho
Summary: The study introduces a novel CAR-NK strategy targeting HLA-G in solid tumors, which shows effective cytolytic action in vitro and in vivo. Combination therapy with low-dose chemotherapy enhances tumor ablation, suggesting a potential wide applicability in treating solid tumors.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Samantha A. Barnes, Katherine M. Audsley, Hannah V. Newnes, Sonia Fernandez, Emma de Jong, Jason Waithman, Bree Foley
Summary: The study found that IFN alpha 14 and IFN beta are superior activators of NK cell effector function in vitro. It was also shown that NK cells pre-activated with IFN alpha 14 significantly prolonged survival in a preclinical model of leukaemia. These results suggest that further investigation into using IFN alpha 14 to modulate NK cells against leukaemia is promising.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Melanie Gauthier, Caroline Laroye, Daniele Bensoussan, Cedric Boura, Veronique Decot
Summary: Monoclonal antibodies targeting tumors and the cooperation with NK cells play a crucial role in enhancing the efficacy of antibody therapy in cancer treatment.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Multidisciplinary Sciences
Timon Damelang, Elizabeth H. Aitken, Wina Hasang, Ester Lopez, Martin Killian, Holger W. Unger, Ali Salanti, Alexis Shub, Elizabeth McCarthy, Katherine Kedzierska, Martha Lappas, Stephen J. Kent, Stephen J. Rogerson, Amy W. Chung
Summary: The study investigated the impact of antibodies in pregnant women on malaria during pregnancy, finding that the anti-inflammatory effect of antibodies during pregnancy may weaken the immune response to placental malaria.
SCIENTIFIC REPORTS
(2021)
Editorial Material
Hematology
Robin Parihar
Summary: In this study, memory-like natural killer (ML NK) cells were evaluated for their potential in treating relapsed acute myeloid leukemia (AML) patients after transplantation. The results show that ML NK cells hold promise in AML therapy, and serial assessments of blood and bone marrow provide new insights into their biology.
Review
Immunology
Nurul Izza Ismail
Summary: As the placenta is semi-allogenic, it is expected that maternal immune cells would attack the invading trophoblast, but studies have shown that they cooperate with the trophoblast to disrupt the arterial wall. uNK cells, unique immune cells, play a role in pregnancy. The interaction between HLA class 1b genes and maternal uNK cells in humans is described in this review.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Debora Basilio-Queiros, Eva Mischak-Weissinger
Summary: Natural Killer (NK) cells have evolved significantly since their initial discovery in the 1970s. Recent research has revealed adaptive-like behavior in NK cells, challenging the traditional categorization of the immune system. This subpopulation of NK cells exhibits characteristics of both innate and adaptive immunity, with clonal-like expansion and enhanced cytotoxic response upon antigen exposure. The implications of these findings are highly relevant in clinical settings, particularly in adoptive immunotherapies where NK cells offer distinct advantages. This review provides an overview of the discovery and current understanding of adaptive NK cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Hematology
Katja Klausz, Michael Cieker, Christian Kellner, Thies Roesner, Anna Otte, Steffen Krohn, Anja Lux, Falk Nimmerjahn, Thomas Valerius, Martin Gramatzki, Matthias Peipp
Summary: The novel therapeutic antibody TP15, targeting ICAM-1, showed significant anti-tumor activity by inducing antibody-dependent cell-mediated cytotoxicity. It prevented myeloma cell engraftment and prolonged survival in a mouse model, demonstrating potential for myeloma immunotherapy.
Article
Oncology
Niklas Baumann, Thies Roesner, J. H. Marco Jansen, Chilam Chan, Klara Marie Eichholz, Katja Klausz, Dorothee Winterberg, Kristina Mueller, Andreas Humpe, Renate Burger, Matthias Peipp, Denis M. Schewe, Christian Kellner, Jeanette H. W. Leusen, Thomas Valerius
Summary: The study shows that inhibiting glutaminyl cyclase can enhance the immunotherapeutic effects on tumor cells. Inhibition of glutaminyl cyclase reduces the specific signal of CD47 at the SIRP alpha binding site, leading to increased efficiency of tumor cell phagocytosis and ADCC reactions mediated by antibodies.
Article
Biochemistry & Molecular Biology
Christian Kellner, Sebastian Lutz, Hans-Heinrich Oberg, Daniela Wesch, Anna Otte, Katarina J. Diemer, Hauke Wilcken, Dirk Bauerschlag, Claus-Christian Glueer, Christian Wichmann, Dieter Kabelitz, Jeanette H. W. Leusen, Katja Klausz, Andreas Humpe, Martin Gramatzki, Matthias Peipp
Summary: Combining NKG2D ligand ULBP2 with HER2-targeting scFv can effectively trigger NK cell killing of HER2-positive breast cancer cells. This immunoligand not only induces tumor cell lysis, but also enhances antibody-dependent cell-mediated cytotoxicity against tumor cells.
BIOLOGICAL CHEMISTRY
(2022)
Meeting Abstract
Hematology
Katja Klausz, Carina Lynn Gehlert, Ammelie Svea Boje, Marta Lustig, Steffen Krohn, Syeda Maliha Ahmed, Christian Kellner, Thomas Valerius, Lenka Besse, Andrej Besse, Christoph Driessen, Martin Gramatzki, Matthias Peipp
Article
Oncology
Katja Klausz, Christian Kellner, Carina Lynn Gehlert, Steffen Krohn, Hauke Wilcken, Inken Floerkemeier, Andreas Guenther, Dirk O. Bauerschlag, Bernd Clement, Martin Gramatzki, Matthias Peipp
Summary: P8-D6 is a novel dual inhibitor that demonstrates broad anti-tumor activity by inhibiting the growth and inducing apoptosis of myeloma cells. It shows low toxicity to healthy cells and significantly inhibits tumor growth in xenograft models. This study highlights the potential of P8-D6 as a promising therapeutic agent for multiple myeloma.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Hematology
Kristina Mueller, Fotini Vogiatzi, Dorothee Winterberg, Thies Rosner, Lennart Lenk, Lorenz Bastian, Carina L. Gehlert, Marie-Pauline Autenrieb, Monika Bruggemann, Gunnar Cario, Martin Schrappe, Andreas E. Kulozik, Cornelia Eckert, Anke K. Bergmann, Beat Bornhauser, Jean-Pierre Bourquin, Thomas Valerius, Matthias Peipp, Christian Kellner, Denis M. Schewe
Summary: This study suggests that combining CD47 blockade with Dara is a promising therapy for T-ALL, especially for relapsed/refractory disease harboring a dismal prognosis in patients.
Review
Immunology
Matthias Peipp, Katja Klausz, Ammelie Svea Boje, Tobias Zeller, Stefan Zielonka, Christian Kellner
Summary: NK cells play a crucial role in cancer immune surveillance by recognizing malignant cells and controlling their activation through the expression of activating and inhibitory receptors. The recruitment and activation of NK cells have great potential in cancer treatment. Targeting the ligands expressed on tumors is also a promising approach to unleash the cytotoxicity of NK cells.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2022)
Article
Immunology
Niklas Baumann, Christian Arndt, Judith Petersen, Marta Lustig, Thies Roesner, Katja Klausz, Christian Kellner, Miriam Bultmann, Lorenz Bastian, Fotini Vogiatzi, Jeanette H. W. Leusen, Renate Burger, Denis M. Schewe, Matthias Peipp, Thomas Valerius
Summary: Antibody-based immunotherapy is increasingly used to treat acute lymphoblastic leukemia (ALL) patients. This study investigates the effects of CD38 antibodies, targeting T-ALL cells expressing CD38, on tumor cell killing through antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cell-mediated cytotoxicity (ADCC). The study shows that IgA2 variants of CD38 antibodies are more effective in killing tumor cells through myeloid cells. The interactions between CD47 and SIRP alpha negatively regulate ADCP and ADCC. Additionally, treatment with all-trans retinoic acid (ATRA) enhances CD38 expression and further enhances ADCP and ADCC.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Fotini Vogiatzi, Julia Heymann, Kristina Muller, Dorothee Winterberg, Aneta Drakul, Thies Rosner, Lennart Lenk, Michelle Heib, Carina Lynn Gehlert, Gunnar Cario, Martin Schrappe, Alexander Claviez, Beat Bornhauser, Jean-Pierre Bourquin, Simon Bomken, Dieter Adam, Fabian-Simon Frielitz, Britta Maecker-Kolhoff, Martin Stanulla, Thomas Valerius, Matthias Peipp, Christian Kellner, Denis M. Schewe
Summary: The addition of the Bcl-2 inhibitor venetoclax enhances the efficacy of therapeutic antibodies by increasing antibody-dependent cellular phagocytosis mediated by macrophages.
Article
Immunology
Carina Lynn Gehlert, Pegah Rahmati, Ammelie Svea Boje, Dorothee Winterberg, Steffen Krohn, Thomas Theocharis, Elisa Cappuzzello, Anja Lux, Falk Nimmerjahn, Ralf J. Ludwig, Marta Lustig, Thies Roesner, Thomas Valerius, Denis Martin Schewe, Christian Kellner, Katja Klausz, Matthias Peipp
Summary: This study engineered a CD19 antibody to enhance effector cell-mediated killing and CDC activity. The dual optimized CD19 antibody showed improved ADCC, ADCP, and CDC compared to the non-engineered antibody. This finding is crucial for improving CD19-directed cancer immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Tobias Zeller, Sebastian Lutz, Ira A. Muennich, Roland Windisch, Patricia Hilger, Tobias Herold, Natyra Tahiri, Jan C. Banck, Oliver Weigert, Andreas Moosmann, Michael Von Bergwelt-Baildon, Cindy Flamann, Heiko Bruns, Christian Wichmann, Niklas Baumann, Thomas Valerius, Denis M. Schewe, Matthias Peipp, Thies Roesner, Andreas Humpe, Christian Kellner
Summary: Blocking both CD47 and LILRB1 can enhance the phagocytosis of lymphoma cells by macrophages, improving the efficacy of antibody therapy for chronic lymphocytic leukemia and lymphomas.
FRONTIERS IN IMMUNOLOGY
(2022)
Meeting Abstract
Hematology
Alexander Biedermann, Doris Mangelberger-Eberl, Dimitrios Mougiakakos, Maike Buettner-Herold, Cindy Flamann, Christian Kellner, Sarah Altmeyer, Joerg Bittenbring, Christian Augsberger, Maria Patra-Kneuer, Karin Landgraf, Kristina Ilieva-Babinsky, Stefan Haskamp, Fabian Beier, Simon Voelkl, Christian Pallasch, Benedikt Jacobs, Stefan Steidl, Christina Heitmueller, Andreas Mackensen, Heiko Bruns
Article
Biotechnology & Applied Microbiology
Adrian Gottschlich, Moritz Thomas, Ruth Gruenmeier, Stefanie Lesch, Lisa Rohrbacher, Veronika Igl, Daria Briukhovetska, Mohamed-Reda Benmebarek, Binje Vick, Sertac Dede, Katharina Mueller, Tao Xu, Dario Dhoqina, Florian Maerkl, Sophie Robinson, Andrea Sendelhofert, Heiko Schulz, Oeykue Umut, Vladyslav Kavaka, Christina Angeliki Tsiverioti, Emanuele Carlini, Sayantan Nandi, Thaddaeus Strzalkowski, Theo Lorenzini, Sophia Stock, Philipp Jie Mueller, Janina Doerr, Matthias Seifert, Bruno L. Cadilha, Ruben Brabenec, Natalie Roeder, Felicitas Rataj, Manuel Nueesch, Franziska Modemann, Jasmin Wellbrock, Walter Fiedler, Christian Kellner, Eduardo Beltran, Tobias Herold, Dominik Paquet, Irmela Jeremias, Louisa von Baumgarten, Stefan Endres, Marion Subklewe, Carsten Marr, Sebastian Kobold
Summary: A single-cell screening approach has identified specific gene targets for CAR-T cell therapy in acute myeloid leukemia (AML). These targets, specifically expressed on malignant cells but lacking on healthy cells, have shown strong efficacy and minimal toxicity in in vitro and in vivo experiments.
NATURE BIOTECHNOLOGY
(2023)
Meeting Abstract
Oncology
A. Gottschlich, M. Thomas, R. Grunmeier, S. Lesch, L. Igl V. Rohrbacher, D. Briukhovetska, M. R. Benmebarek, S. Dede, K. Muller, T. Xu, D. Dhoqina, O. Umut, F. Markl, S. Robinson, H. Schulz, B. Vick, B. Cadilha, R. Brabenec, N. Roder, F. Rataj, M. Nuesch, J. Wellbrock, F. Modemann, W. Fiedler, C. Kellner, D. Paquet, I. Jeremias, L. Von Baumgarten, S. Endres, M. Subklewe, C. Marc, S. Kobold
ONCOLOGY RESEARCH AND TREATMENT
(2022)
Meeting Abstract
Oncology
P. Hilger, T. Zeller, F. Vogiatzi, K. Mueller, I. A. Muennich, R. Windisch, C. Wichmann, F. Nimmerjahn, T. Valerius, M. Peipp, A. Humpe, D. M. Schewe, C. Kellner
ONCOLOGY RESEARCH AND TREATMENT
(2022)