Journal Article
. 2012 Sep; 120(22):4317-23.
doi: 10.1182/blood-2012-06-437558.

A phase 1 trial of the anti-inhibitory KIR mAb IPH2101 for AML in complete remission

Norbert Vey 1 Jean-Henri Bourhis  Nicolas Boissel  Dominique Bordessoule  Thomas Prebet  Aude Charbonnier  Anne Etienne  Pascale Andre  François Romagne  Don Benson  Herve Dombret  Daniel Olive  
  • PMID: 23002117
  •     139 citations


IPH2101 is an anti-killer inhibitory receptor (anti-KIR) mAb that can block KIR-mediated inhibition of natural killer (NK) cells to enhance cytotoxicity against acute myeloid leukemia blasts. We have conducted a phase 1 study of IPH2101 in elderly patients with acute myeloid leukemia in first complete remission. Patients received escalating doses (0.0003-3 mg/kg) of IPH2101 following a 3 + 3 design. Safety, toxicity (primary end points), pharmacokinetics, outcome, and immunologic correlates were evaluated. Twenty-three patients (median age, 71 years), were enrolled. Adverse events were mild and transient, consisting mainly of infusion syndrome and erythema. The maximum tolerated dose was not reached, although full KIR saturation (> 90%) was sustained for more than 2 weeks at 1 and 3 mg/kg. There was a clear correlation between mAb exposure and KIR occupancy. Neither hematologic toxicity nor significant changes in the numbers and distribution of lymphocyte subsets, NK cell receptor expression, or in vitro cytotoxicity were seen. At the highest dose levels (0.3, 1, and 3 mg/kg), transient increases in TNF-α and MIP-1β serum concentrations and NK cell CD69 expression were observed. Overall and relapse-free survival in the present study compared favorably to reports in comparable patient populations. We conclude that IPH2101 administration is safe and can block KIR for prolonged periods of time with limited side effects. Registered with the European Union Drug Regulating Authorities Clinical Trials (EUDRACT) as 2005-005298-31.

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Ana Stojanovic, Margareta P Correia, Adelheid Cerwenka.
Cancer Microenviron, 2012 Dec 18; 6(2). PMID: 23242671    Free PMC article.
The TNF receptor-ligands 4-1BB-4-1BBL and GITR-GITRL in NK cell responses.
Isabel Barao.
Front Immunol, 2013 Jan 15; 3. PMID: 23316193    Free PMC article.
Emerging immunotherapies in older adults with acute myeloid leukemia.
Sumithira Vasu, William Blum.
Curr Opin Hematol, 2013 Jan 22; 20(2). PMID: 23334192    Free PMC article.
8(th) Annual European Antibody Congress 2012: November 27-28, 2012, Geneva, Switzerland.
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Immunity of human epithelial ovarian carcinoma: the paradigm of immune suppression in cancer.
Vincent Lavoué, Aurélie Thédrez, +6 authors, Florian Cabillic.
J Transl Med, 2013 Jun 15; 11. PMID: 23763830    Free PMC article.
Natural killer cell biology: an update and future directions.
Kerry S Campbell, Jun Hasegawa.
J Allergy Clin Immunol, 2013 Aug 03; 132(3). PMID: 23906377    Free PMC article.
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Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies.
Holbrook E Kohrt, Ariane Thielens, +14 authors, Pascale André.
Blood, 2013 Dec 12; 123(5). PMID: 24326534    Free PMC article.
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J Nakata, K Nakano, +16 authors, N Hosen.
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Hunting for clinical translation with innate-like immune cells and their receptors.
W Scheper, C Gründer, +2 authors, J Kuball.
Leukemia, 2013 Dec 19; 28(6). PMID: 24345790
Natural killer cells modulation in hematological malignancies.
Céline Baier, Aurore Fino, +4 authors, Régis T Costello.
Front Immunol, 2014 Jan 07; 4. PMID: 24391641    Free PMC article.
Combination immune therapies to enhance anti-tumor responses by NK cells.
Ashley Mentlik James, Adam D Cohen, Kerry S Campbell.
Front Immunol, 2014 Jan 07; 4. PMID: 24391651    Free PMC article.
Potential of new therapies like anti-PD1 in kidney cancer.
Anasuya Gunturi, David F McDermott.
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Bree Foley, Martin Felices, +3 authors, Jeffrey S Miller.
Immunol Rev, 2014 Feb 13; 258(1). PMID: 24517425    Free PMC article.
Killer immunoglobulin-like receptors and tumor immunity.
Don M Benson, Michael A Caligiuri.
Cancer Immunol Res, 2014 Mar 05; 2(2). PMID: 24592397    Free PMC article.
NK cell self tolerance, responsiveness and missing self recognition.
Nataliya Shifrin, David H Raulet, Michele Ardolino.
Semin Immunol, 2014 Mar 19; 26(2). PMID: 24629893    Free PMC article.
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Haematologica, 2014 Mar 25; 99(6). PMID: 24658821    Free PMC article.
Trial Watch: Immunostimulatory monoclonal antibodies in cancer therapy.
Fernando Aranda, Erika Vacchelli, +5 authors, Lorenzo Galluzzi.
Oncoimmunology, 2014 Apr 05; 3(1). PMID: 24701370    Free PMC article.
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Front Immunol, 2014 Apr 10; 5. PMID: 24715892    Free PMC article.
Ly49 receptors: innate and adaptive immune paradigms.
Mir Munir A Rahim, Megan M Tu, +4 authors, Andrew P Makrigiannis.
Front Immunol, 2014 Apr 26; 5. PMID: 24765094    Free PMC article.
Dok1 and Dok2 proteins regulate natural killer cell development and function.
Javier Celis-Gutierrez, Marilyn Boyron, +6 authors, Jacques A Nunès.
EMBO J, 2014 Jun 26; 33(17). PMID: 24963146    Free PMC article.
Immunotherapy in pediatric malignancies: current status and future perspectives.
Christian M Capitini, Mario Otto, Kenneth B DeSantes, Paul M Sondel.
Future Oncol, 2014 Aug 26; 10(9). PMID: 25145434    Free PMC article.
Immune checkpoint inhibitors in clinical trials.
Elad Sharon, Howard Streicher, Priscila Goncalves, Helen X Chen.
Chin J Cancer, 2014 Sep 06; 33(9). PMID: 25189716    Free PMC article.
NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma.
Cheng Sun, Haoyu Sun, Cai Zhang, Zhigang Tian.
Cell Mol Immunol, 2014 Oct 14; 12(3). PMID: 25308752    Free PMC article.
New strategies in acute myelogenous leukemia: leukemogenesis and personalized medicine.
Ivana Gojo, Judith E Karp.
Clin Cancer Res, 2014 Oct 18; 20(24). PMID: 25324141    Free PMC article.
Cytokine therapy reverses NK cell anergy in MHC-deficient tumors.
Michele Ardolino, Camillia S Azimi, +8 authors, David H Raulet.
J Clin Invest, 2014 Oct 21; 124(11). PMID: 25329698    Free PMC article.
Highly Cited.
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Mustafa Diken, Sebastian Boegel, +6 authors, Sebastian Kreiter.
Hum Vaccin Immunother, 2014 Dec 09; 10(10). PMID: 25483671    Free PMC article.
OX40 Agonists and Combination Immunotherapy: Putting the Pedal to the Metal.
Stefanie N Linch, Michael J McNamara, William L Redmond.
Front Oncol, 2015 Mar 13; 5. PMID: 25763356    Free PMC article.
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Haematological malignancies: at the forefront of immunotherapeutic innovation.
Pavan Bachireddy, Ute E Burkhardt, Mohini Rajasagi, Catherine J Wu.
Nat Rev Cancer, 2015 Mar 20; 15(4). PMID: 25786696    Free PMC article.
Natural killer cell therapy in children with relapsed leukemia.
Jeffrey E Rubnitz, Hiroto Inaba, +8 authors, Wing Leung.
Pediatr Blood Cancer, 2015 May 01; 62(8). PMID: 25925135    Free PMC article.
Therapeutic potential and challenges of natural killer cells in treatment of solid tumors.
Andrea Gras Navarro, Andreas T Björklund, Martha Chekenya.
Front Immunol, 2015 May 15; 6. PMID: 25972872    Free PMC article.
Highly Cited. Review.
New approaches for the immunotherapy of acute myeloid leukemia.
Terrence L Geiger, Jeffrey E Rubnitz.
Discov Med, 2015 May 16; 19(105). PMID: 25977190    Free PMC article.
Orchestrating an immune response against cancer with engineered immune cells expressing αβTCRs, CARs, and innate immune receptors: an immunological and regulatory challenge.
Moniek A de Witte, Guido J J Kierkels, +2 authors, Jürgen Kuball.
Cancer Immunol Immunother, 2015 May 21; 64(7). PMID: 25990073    Free PMC article.
Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies.
Gianfranco Pittari, Perla Filippini, +2 authors, Sergio Rutella.
Front Immunol, 2015 Jun 02; 6. PMID: 26029215    Free PMC article.
Natural killer cell dysfunction in hepatocellular carcinoma and NK cell-based immunotherapy.
Cheng Sun, Hao-yu Sun, +2 authors, Zhi-gang Tian.
Acta Pharmacol Sin, 2015 Jun 16; 36(10). PMID: 26073325    Free PMC article.
Present and Future of Allogeneic Natural Killer Cell Therapy.
Okjae Lim, Mi Young Jung, Yu Kyeong Hwang, Eui-Cheol Shin.
Front Immunol, 2015 Jun 20; 6. PMID: 26089823    Free PMC article.
Evolving synergistic combinations of targeted immunotherapies to combat cancer.
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Nat Rev Cancer, 2015 Jul 25; 15(8). PMID: 26205340
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Combination cancer immunotherapy and new immunomodulatory targets.
Kathleen M Mahoney, Paul D Rennert, Gordon J Freeman.
Nat Rev Drug Discov, 2015 Aug 01; 14(8). PMID: 26228759
Highly Cited. Review.
Cytokine treatment in cancer immunotherapy.
Michele Ardolino, Joy Hsu, David H Raulet.
Oncotarget, 2015 Aug 26; 6(23). PMID: 26305981    Free PMC article.
Strategies for combining immunotherapy with radiation for anticancer therapy.
Steven N Seyedin, Jonathan E Schoenhals, +14 authors, James W Welsh.
Immunotherapy, 2015 Aug 28; 7(9). PMID: 26310908    Free PMC article.
Immune Modulation in Hematologic Malignancies.
Madhav V Dhodapkar, Kavita M Dhodapkar.
Semin Oncol, 2015 Sep 01; 42(4). PMID: 26320065    Free PMC article.
How to outsmart NK cell tolerance.
Grzegorz Terszowski, Christian Klein, Laurent Schmied, Martin Stern.
Oncoimmunology, 2015 Sep 26; 4(9). PMID: 26405590    Free PMC article.
Improving natural killer cell cancer immunotherapy.
Melissa M Berrien-Elliott, Rizwan Romee, Todd A Fehniger.
Curr Opin Organ Transplant, 2015 Sep 29; 20(6). PMID: 26414502    Free PMC article.
Selection of an HLA-C*03:04-Restricted HIV-1 p24 Gag Sequence Variant Is Associated with Viral Escape from KIR2DL3+ Natural Killer Cells: Data from an Observational Cohort in South Africa.
Angelique Hölzemer, Christina F Thobakgale, +19 authors, Marcus Altfeld.
PLoS Med, 2015 Nov 18; 12(11). PMID: 26575988    Free PMC article.
Identification of Anti-tumor Cells Carrying Natural Killer (NK) Cell Antigens in Patients With Hematological Cancers.
Ewelina Krzywinska, Nerea Allende-Vega, +9 authors, Martin Villalba.
EBioMedicine, 2015 Dec 03; 2(10). PMID: 26629531    Free PMC article.
The Application of Natural Killer Cell Immunotherapy for the Treatment of Cancer.
Katayoun Rezvani, Rayne H Rouce.
Front Immunol, 2015 Dec 05; 6. PMID: 26635792    Free PMC article.
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NK cells and cancer: you can teach innate cells new tricks.
Maelig G Morvan, Lewis L Lanier.
Nat Rev Cancer, 2015 Dec 24; 16(1). PMID: 26694935
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Natural Killer Cell Immunomodulation: Targeting Activating, Inhibitory, and Co-stimulatory Receptor Signaling for Cancer Immunotherapy.
Cariad Chester, Katherine Fritsch, Holbrook E Kohrt.
Front Immunol, 2015 Dec 24; 6. PMID: 26697006    Free PMC article.
Effects of anti-NKG2A antibody administration on leukemia and normal hematopoietic cells.
Loredana Ruggeri, Elena Urbani, +8 authors, Andrea Velardi.
Haematologica, 2016 Jan 02; 101(5). PMID: 26721894    Free PMC article.
Highly Cited.
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V Naranbhai, D de Assis Rosa, +14 authors, T Ndung'u.
BMC Infect Dis, 2016 Jan 27; 16. PMID: 26809736    Free PMC article.
Cytokine therapy restores antitumor responses of NK cells rendered anergic in MHC I-deficient tumors.
Michele Ardolino, David H Raulet.
Oncoimmunology, 2016 Mar 05; 5(1). PMID: 26942049    Free PMC article.
Underground Adaptation to a Hostile Environment: Acute Myeloid Leukemia vs. Natural Killer Cells.
Nicolas Dulphy, Anne-Sophie Chrétien, +6 authors, Antoine Toubert.
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CD45 Isoform Profile Identifies Natural Killer (NK) Subsets with Differential Activity.
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PLoS One, 2016 Apr 23; 11(4). PMID: 27100180    Free PMC article.
Targeting NK Cells for Anticancer Immunotherapy: Clinical and Preclinical Approaches.
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Licensed and Unlicensed NK Cells: Differential Roles in Cancer and Viral Control.
Megan M Tu, Ahmad Bakur Mahmoud, Andrew P Makrigiannis.
Front Immunol, 2016 May 21; 7. PMID: 27199990    Free PMC article.
Targeting KIR Blockade in Multiple Myeloma: Trouble in Checkpoint Paradise?
Martin Felices, Jeffrey S Miller.
Clin Cancer Res, 2016 Nov 03; 22(21). PMID: 27430580    Free PMC article.
Enhancement of antibody-dependent cell mediated cytotoxicity: a new era in cancer treatment.
Narendiran Rajasekaran, Cariad Chester, +2 authors, Holbrook E Kohrt.
Immunotargets Ther, 2015 Jan 01; 4. PMID: 27471715    Free PMC article.
Targeting natural killer cells in cancer immunotherapy.
Camille Guillerey, Nicholas D Huntington, Mark J Smyth.
Nat Immunol, 2016 Aug 20; 17(9). PMID: 27540992
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Features of Memory-Like and PD-1(+) Human NK Cell Subsets.
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Rajarsi Mandal, Yasin Şenbabaoğlu, +8 authors, Luc Gt Morris.
JCI Insight, 2016 Oct 26; 1(17). PMID: 27777979    Free PMC article.
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M Ilander, U Olsson-Strömberg, +28 authors, S Mustjoki.
Leukemia, 2016 Nov 29; 31(5). PMID: 27890936    Free PMC article.
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Manufacturing Natural Killer Cells as Medicinal Products.
Christian Chabannon, Bechara Mfarrej, +5 authors, Boris Calmels.
Front Immunol, 2016 Nov 30; 7. PMID: 27895646    Free PMC article.
The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia.
Michael Boyiadzis, Michael R Bishop, +45 authors, Madhav V Dhodapkar.
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NKp30 expression is a prognostic immune biomarker for stratification of patients with intermediate-risk acute myeloid leukemia.
Anne-Sophie Chretien, Cyril Fauriat, +16 authors, Daniel Olive.
Oncotarget, 2017 May 27; 8(30). PMID: 28548938    Free PMC article.
Patient's Natural Killer Cells in the Era of Targeted Therapies: Role for Tumor Killers.
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Zachary B Davis, Daniel A Vallera, Jeffrey S Miller, Martin Felices.
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Sourav Paul, Girdhari Lal.
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Norbert Vey, Lionel Karlin, +11 authors, Anthony Gonçalves.
Oncotarget, 2018 May 01; 9(25). PMID: 29707140    Free PMC article.
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O Adotevi, Y Godet, +18 authors, C Borg.
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Theranostics, 2018 Aug 08; 8(14). PMID: 30083264    Free PMC article.
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TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer.
Alexandre Ivagnès, Meriem Messaoudene, +23 authors, Laurence Zitvogel.
Oncoimmunology, 2017 Oct 11; 7(12). PMID: 30524877    Free PMC article.
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Haoyu Sun, Cheng Sun.
Front Immunol, 2019 Nov 05; 10. PMID: 31681269    Free PMC article.
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Immunotherapy for acute myeloid leukemia: from allogeneic stem cell transplant to novel therapeutics.
David A Knorr, Aaron D Goldberg, Eytan M Stein, Martin S Tallman.
Leuk Lymphoma, 2019 Jul 25; 60(14). PMID: 31335250    Free PMC article.
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Paola Minetto, Fabio Guolo, +7 authors, Emanuela Marcenaro.
Front Immunol, 2019 Dec 24; 10. PMID: 31867006    Free PMC article.
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Emily J Pomeroy, John T Hunzeker, +13 authors, Branden S Moriarity.
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Martin Villalba, Catherine Alexia, +2 authors, Delphine Gitenay.
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Front Immunol, 2019 Jun 20; 10. PMID: 31214193    Free PMC article.
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Highly Cited. Review.
Natural Killer Cells: Tumor Surveillance and Signaling.
Lizeth G Meza Guzman, Narelle Keating, Sandra E Nicholson.
Cancers (Basel), 2020 Apr 16; 12(4). PMID: 32290478    Free PMC article.
Checkpoint Inhibitors and Engineered Cells: New Weapons for Natural Killer Cell Arsenal Against Hematological Malignancies.
Massimo Giuliani, Alessandro Poggi.
Cells, 2020 Jul 03; 9(7). PMID: 32610578    Free PMC article.
Harnessing NK Cell Checkpoint-Modulating Immunotherapies.
Sachin Kumar Singh Chauhan, Ulrike Koehl, Stephan Kloess.
Cancers (Basel), 2020 Jul 10; 12(7). PMID: 32640575    Free PMC article.
Targeting immune checkpoints in hematological malignancies.
Basit Salik, Mark J Smyth, Kyohei Nakamura.
J Hematol Oncol, 2020 Aug 14; 13(1). PMID: 32787882    Free PMC article.
Natural Killer Cells as Key Players of Tumor Progression and Angiogenesis: Old and Novel Tools to Divert Their Pro-Tumor Activities into Potent Anti-Tumor Effects.
Barbara Bassani, Denisa Baci, +3 authors, Lorenzo Mortara.
Cancers (Basel), 2019 Apr 04; 11(4). PMID: 30939820    Free PMC article.
NK-mediated antibody-dependent cell-mediated cytotoxicity in solid tumors: biological evidence and clinical perspectives.
Cristiana Lo Nigro, Marco Macagno, +3 authors, Marco Carlo Merlano.
Ann Transl Med, 2019 Apr 26; 7(5). PMID: 31019955    Free PMC article.
Strategies to Augment Natural Killer (NK) Cell Activity against Solid Tumors.
Ziqing Chen, Ying Yang, Lisa L Liu, Andreas Lundqvist.
Cancers (Basel), 2019 Jul 26; 11(7). PMID: 31340613    Free PMC article.
Improving the Clinical Application of Natural Killer Cells by Modulating Signals Signal from Target Cells.
Monika Holubova, Martin Leba, +3 authors, Daniel Lysak.
Int J Mol Sci, 2019 Jul 18; 20(14). PMID: 31311121    Free PMC article.
Natural killer cell-based immunotherapy for acute myeloid leukemia.
Jing Xu, Ting Niu.
J Hematol Oncol, 2020 Dec 09; 13(1). PMID: 33287858    Free PMC article.
NK cells for cancer immunotherapy.
Noriko Shimasaki, Amit Jain, Dario Campana.
Nat Rev Drug Discov, 2020 Jan 08; 19(3). PMID: 31907401
TRIGGERED: could refocused cell signaling be key to natural killer cell-based HIV immunotherapeutics?
Sho Sugawara, Cordelia Manickam, R Keith Reeves.
AIDS, 2020 Oct 30; 35(2). PMID: 33116071    Free PMC article.
Exploring the NK cell platform for cancer immunotherapy.
Jacob A Myers, Jeffrey S Miller.
Nat Rev Clin Oncol, 2020 Sep 17; 18(2). PMID: 32934330    Free PMC article.
Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors.
Nayoung Kim, Dong-Hee Lee, +5 authors, Hun Sik Kim.
BMB Rep, 2020 Dec 11; 54(1). PMID: 33298244    Free PMC article.
Update of early phase clinical trials in cancer immunotherapy.
Dae Ho Lee.
BMB Rep, 2021 Jan 08; 54(1). PMID: 33407992    Free PMC article.
Killing the Invaders: NK Cell Impact in Tumors and Anti-Tumor Therapy.
Martina Molgora, Victor S Cortez, Marco Colonna.
Cancers (Basel), 2021 Feb 07; 13(4). PMID: 33546248    Free PMC article.
Natural killer cell therapy for hematologic malignancies: successes, challenges, and the future.
Margaret G Lamb, Hemalatha G Rangarajan, Brian P Tullius, Dean A Lee.
Stem Cell Res Ther, 2021 Mar 27; 12(1). PMID: 33766099    Free PMC article.
The Advances and Challenges of NK Cell-Based Cancer Immunotherapy.
Synat Kang, Xuefeng Gao, +3 authors, Li Yu.
Curr Oncol, 2021 Mar 04; 28(2). PMID: 33652996    Free PMC article.
Enhancing a Natural Killer: Modification of NK Cells for Cancer Immunotherapy.
Rasa Islam, Aleta Pupovac, +4 authors, Alan Trounson.
Cells, 2021 May 06; 10(5). PMID: 33946954    Free PMC article.
Fc-engineered anti-CD33 monoclonal antibody potentiates cytotoxicity of membrane-bound interleukin-21 expanded natural killer cells in acute myeloid leukemia.
Rajeswaran Mani, Girish Rajgolikar, +7 authors, Sumithira Vasu.
Cytotherapy, 2020 Apr 19; 22(7). PMID: 32303428    Free PMC article.
The "Magic Bullet" Is Here? Cell-Based Immunotherapies for Hematological Malignancies in the Twilight of the Chemotherapy Era.
Nina Miazek-Zapala, Aleksander Slusarczyk, +4 authors, Malgorzata Bobrowicz.
Cells, 2021 Jul 03; 10(6). PMID: 34203935    Free PMC article.
Optimizing NK Cell-Based Immunotherapy in Myeloid Leukemia: Abrogating an Immunosuppressive Microenvironment.
Natasha Mupeta Kaweme, Fuling Zhou.
Front Immunol, 2021 Jul 06; 12. PMID: 34220833    Free PMC article.
Natural Killer Cells and Type 1 Innate Lymphoid Cells in Hepatocellular Carcinoma: Current Knowledge and Future Perspectives.
Nicolas Jacquelot, Cyril Seillet, +3 authors, Pamela S Ohashi.
Int J Mol Sci, 2021 Aug 28; 22(16). PMID: 34445750    Free PMC article.
The Biological Role and Therapeutic Potential of NK Cells in Hematological and Solid Tumors.
Rodion A Velichinskii, Maria A Streltsova, +2 authors, Elena I Kovalenko.
Int J Mol Sci, 2021 Nov 14; 22(21). PMID: 34768814    Free PMC article.
Natural killer cells and immune-checkpoint inhibitor therapy: Current knowledge and new challenges.
Alessandro Poggi, Maria Raffaella Zocchi.
Mol Ther Oncolytics, 2022 Jan 04; 24. PMID: 34977340    Free PMC article.
Challenges and Recent Advances in NK Cell-Targeted Immunotherapies in Solid Tumors.
Guangyu Lian, Thomas Shiu-Kwong Mak, Xueqing Yu, Hui-Yao Lan.
Int J Mol Sci, 2022 Jan 12; 23(1). PMID: 35008589    Free PMC article.
Natural Killer Cell-Mediated Immunotherapy for Leukemia.
Michaela Allison, Joel Mathews, Taylor Gilliland, Stephen O Mathew.
Cancers (Basel), 2022 Feb 16; 14(3). PMID: 35159109    Free PMC article.
Lirilumab and Avelumab Enhance Anti-HPV+ Cervical Cancer Activity of Natural Killer Cells via Vav1-Dependent NF-κB Disinhibition.
Hongli Liu, Sihui Zhou, +7 authors, Nan Wu.
Front Oncol, 2022 Feb 18; 12. PMID: 35174079    Free PMC article.
Blockade of inhibitory killer cell immunoglobulin-like receptors and IL-2 triggering reverses the functional hypoactivity of tumor-derived NK-cells in glioblastomas.
Cüneyt Sönmez, Johannes Wölfer, +6 authors, Oliver M Grauer.
Sci Rep, 2022 Apr 28; 12(1). PMID: 35474089    Free PMC article.
Natural killer cells: a promising immunotherapy for cancer.
Junfeng Chu, Fengcai Gao, +4 authors, Yanyan Liu.
J Transl Med, 2022 May 24; 20(1). PMID: 35606854
Natural killer cells and acute myeloid leukemia: promises and challenges.
Shayan Rahmani, Niloufar Yazdanpanah, Nima Rezaei.
Cancer Immunol Immunother, 2022 Jun 01;. PMID: 35639116