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

Affiliations

¹ Institut Paoli-Calmettes, Marseille, France. veyn@ipc.unicancer.fr

PMID: 23002117
139 citations

Abstract

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.

Other Links

Full text on Blood

Cited By

Citedby
Shaping of NK cell responses by the tumor microenvironment. 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. Review.
8(th) Annual European Antibody Congress 2012: November 27-28, 2012, Geneva, Switzerland. Alain Beck, Paul J Carter, +5 authors, Robert Mabry. less MAbs, 2013 Mar 16; 5(3). PMID: 23493119 Free PMC article.
Immunity of human epithelial ovarian carcinoma: the paradigm of immune suppression in cancer. Vincent Lavoué, Aurélie Thédrez, +6 authors, Florian Cabillic. less J Transl Med, 2013 Jun 15; 11. PMID: 23763830 Free PMC article. Review.
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. Highly Cited. Review.
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. less Blood, 2013 Dec 12; 123(5). PMID: 24326534 Free PMC article. Highly Cited.
In vivo eradication of MLL/ENL leukemia cells by NK cells in the absence of adaptive immunity. J Nakata, K Nakano, +16 authors, N Hosen. less Leukemia, 2013 Dec 18; 28(6). PMID: 24336127
Hunting for clinical translation with innate-like immune cells and their receptors. W Scheper, C Gründer, +2 authors, T Straetemans, Z Sebestyen, J Kuball. less Leukemia, 2013 Dec 19; 28(6). PMID: 24345790 Review.
Natural killer cells modulation in hematological malignancies. Céline Baier, Aurore Fino, +4 authors, Régis T Costello. less 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. Curr Treat Options Oncol, 2014 Feb 08; 15(1). PMID: 24504486 Review.
The biology of NK cells and their receptors affects clinical outcomes after hematopoietic cell transplantation (HCT). Bree Foley, Martin Felices, +3 authors, Jeffrey S Miller. less Immunol Rev, 2014 Feb 13; 258(1). PMID: 24517425 Free PMC article. Review.
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. Review.
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. Highly Cited. Review.
A phase II trial of pan-KIR2D blockade with IPH2101 in smoldering multiple myeloma. Neha Korde, Mattias Carlsten, +20 authors, Ola Landgren. less 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. less Oncoimmunology, 2014 Apr 05; 3(1). PMID: 24701370 Free PMC article. Highly Cited.
Cancer-Induced Alterations of NK-Mediated Target Recognition: Current and Investigational Pharmacological Strategies Aiming at Restoring NK-Mediated Anti-Tumor Activity. Anne-Sophie Chretien, Aude Le Roy, +4 authors, Daniel Olive. less Front Immunol, 2014 Apr 10; 5. PMID: 24715892 Free PMC article. Review.
Ly49 receptors: innate and adaptive immune paradigms. Mir Munir A Rahim, Megan M Tu, +4 authors, Andrew P Makrigiannis. less Front Immunol, 2014 Apr 26; 5. PMID: 24765094 Free PMC article. Review.
Dok1 and Dok2 proteins regulate natural killer cell development and function. Javier Celis-Gutierrez, Marilyn Boyron, +6 authors, Jacques A Nunès. less 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. Review.
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. Review.
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. Review.
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. Review.
Cytokine therapy reverses NK cell anergy in MHC-deficient tumors. Michele Ardolino, Camillia S Azimi, +8 authors, David H Raulet. less J Clin Invest, 2014 Oct 21; 124(11). PMID: 25329698 Free PMC article. Highly Cited.
CIMT 2014: Next waves in cancer immunotherapy--report on the 12th annual meeting of the Association for Cancer Immunotherapy: May 6–8 2014, Mainz, Germany. Mustafa Diken, Sebastian Boegel, +6 authors, Sebastian Kreiter. less 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. Highly Cited. Review.
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. Review.
Natural killer cell therapy in children with relapsed leukemia. Jeffrey E Rubnitz, Hiroto Inaba, +8 authors, Wing Leung. less 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. Review.
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, Trudy Straetemans, Cedrik M Britten, Jürgen Kuball. less Cancer Immunol Immunother, 2015 May 21; 64(7). PMID: 25990073 Free PMC article. Review.
Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies. Gianfranco Pittari, Perla Filippini, +2 authors, Sergio Rutella. less Front Immunol, 2015 Jun 02; 6. PMID: 26029215 Free PMC article. Review.
Natural killer cell dysfunction in hepatocellular carcinoma and NK cell-based immunotherapy. Cheng Sun, Hao-yu Sun, +2 authors, Wei-hua Xiao, Cai Zhang, Zhi-gang Tian. less Acta Pharmacol Sin, 2015 Jun 16; 36(10). PMID: 26073325 Free PMC article. Review.
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. Review.
Evolving synergistic combinations of targeted immunotherapies to combat cancer. Ignacio Melero, David M Berman, +3 authors, John Haanen. less Nat Rev Cancer, 2015 Jul 25; 15(8). PMID: 26205340 Highly Cited. Review.
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. less Immunotherapy, 2015 Aug 28; 7(9). PMID: 26310908 Free PMC article. Review.
Immune Modulation in Hematologic Malignancies. Madhav V Dhodapkar, Kavita M Dhodapkar. Semin Oncol, 2015 Sep 01; 42(4). PMID: 26320065 Free PMC article. Review.
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. Review.
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. less 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. less 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. Highly Cited. Review.
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 Highly Cited. Review.
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. Review.
Effects of anti-NKG2A antibody administration on leukemia and normal hematopoietic cells. Loredana Ruggeri, Elena Urbani, +8 authors, Andrea Velardi. less Haematologica, 2016 Jan 02; 101(5). PMID: 26721894 Free PMC article. Highly Cited.
Killer-cell Immunoglobulin-like Receptor (KIR) gene profiles modify HIV disease course, not HIV acquisition in South African women. V Naranbhai, D de Assis Rosa, +14 authors, T Ndung'u. less 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. less Front Immunol, 2016 Mar 26; 7. PMID: 27014273 Free PMC article. Review.
CD45 Isoform Profile Identifies Natural Killer (NK) Subsets with Differential Activity. Ewelina Krzywinska, Amelie Cornillon, +12 authors, Martin Villalba. less PLoS One, 2016 Apr 23; 11(4). PMID: 27100180 Free PMC article.
Targeting NK Cells for Anticancer Immunotherapy: Clinical and Preclinical Approaches. Sebastian Carotta. Front Immunol, 2016 May 06; 7. PMID: 27148271 Free PMC article. Review.
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. Review.
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, Atsushi Yonezawa, Xing Zhao, Holbrook E Kohrt. less Immunotargets Ther, 2015 Jan 01; 4. PMID: 27471715 Free PMC article. Review.
Targeting natural killer cells in cancer immunotherapy. Camille Guillerey, Nicholas D Huntington, Mark J Smyth. Nat Immunol, 2016 Aug 20; 17(9). PMID: 27540992 Highly Cited. Review.
Features of Memory-Like and PD-1(+) Human NK Cell Subsets. Mariella Della Chiesa, Silvia Pesce, +4 authors, Emanuela Marcenaro. less Front Immunol, 2016 Sep 30; 7. PMID: 27683578 Free PMC article. Highly Cited. Review.
Human NK Cell Subsets Redistribution in Pathological Conditions: A Role for CCR7 Receptor. Silvia Pesce, Lorenzo Moretta, Alessandro Moretta, Emanuela Marcenaro. Front Immunol, 2016 Oct 25; 7. PMID: 27774094 Free PMC article. Review.
The head and neck cancer immune landscape and its immunotherapeutic implications. Rajarsi Mandal, Yasin Şenbabaoğlu, +8 authors, Luc Gt Morris. less JCI Insight, 2016 Oct 26; 1(17). PMID: 27777979 Free PMC article. Highly Cited.
Flow Cytometry-based Assay for the Monitoring of NK Cell Functions. Sara Tognarelli, Benedikt Jacobs, Nina Staiger, Evelyn Ullrich. J Vis Exp, 2016 Nov 15; (116). PMID: 27842341 Free PMC article.
Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia. M Ilander, U Olsson-Strömberg, +28 authors, S Mustjoki. less Leukemia, 2016 Nov 29; 31(5). PMID: 27890936 Free PMC article. Highly Cited.
Immunological and Translational Aspects of NK Cell-Based Antitumor Immunotherapies. Maxim Shevtsov, Gabriele Multhoff. Front Immunol, 2016 Nov 29; 7. PMID: 27891129 Free PMC article. Review.
Manufacturing Natural Killer Cells as Medicinal Products. Christian Chabannon, Bechara Mfarrej, +5 authors, Boris Calmels. less Front Immunol, 2016 Nov 30; 7. PMID: 27895646 Free PMC article. Review.
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. less J Immunother Cancer, 2016 Dec 27; 4. PMID: 28018601 Free PMC article.
Kinetics of Cytotoxic Lymphocytes Reconstitution after Induction Chemotherapy in Elderly AML Patients Reveals Progressive Recovery of Normal Phenotypic and Functional Features in NK Cells. Jérôme Rey, Cyril Fauriat, +8 authors, Daniel Olive. less Front Immunol, 2017 Feb 18; 8. PMID: 28210257 Free PMC article.
Molecular checkpoints controlling natural killer cell activation and their modulation for cancer immunotherapy. Hyung-Joon Kwon, Nayoung Kim, Hun Sik Kim. Exp Mol Med, 2017 Apr 01; 49(3). PMID: 28360428 Free PMC article. Review.
Role of Natural Killer Cells in HIV-Associated Malignancies. Fabio E Leal, Thomas A Premeaux, Mohamed Abdel-Mohsen, Lishomwa C Ndhlovu. Front Immunol, 2017 Apr 06; 8. PMID: 28377768 Free PMC article. Review.
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. less 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. Meriem Messaoudene, Alexandra Frazao, +3 authors, Anne Caignard. less Front Immunol, 2017 Jul 01; 8. PMID: 28659921 Free PMC article.
Natural killer cells unleashed: Checkpoint receptor blockade and BiKE/TriKE utilization in NK-mediated anti-tumor immunotherapy. Zachary B Davis, Daniel A Vallera, Jeffrey S Miller, Martin Felices. Semin Immunol, 2017 Sep 09; 31. PMID: 28882429 Free PMC article. Review.
The Molecular Mechanism of Natural Killer Cells Function and Its Importance in Cancer Immunotherapy. Sourav Paul, Girdhari Lal. Front Immunol, 2017 Sep 29; 8. PMID: 28955340 Free PMC article. Highly Cited. Review.
Generation of "Off-the-Shelf" Natural Killer Cells from Peripheral Blood Cell-Derived Induced Pluripotent Stem Cells. Jieming Zeng, Shin Yi Tang, Lai Ling Toh, Shu Wang. Stem Cell Reports, 2017 Nov 28; 9(6). PMID: 29173894 Free PMC article.
Strategies to activate NK cells to prevent relapse and induce remission following hematopoietic stem cell transplantation. Sarah Cooley, Peter Parham, Jeffrey S Miller. Blood, 2018 Jan 24; 131(10). PMID: 29358179 Free PMC article. Highly Cited. Review.
Monoclonal Antibody Therapies for Hematological Malignancies: Not Just Lineage-Specific Targets. Carlos Cuesta-Mateos, Ana Alcaraz-Serna, Beatriz Somovilla-Crespo, Cecilia Muñoz-Calleja. Front Immunol, 2018 Feb 02; 8. PMID: 29387053 Free PMC article. Review.
Strategies for clinical development of monoclonal antibodies beyond first-in-human trials: tested doses and rationale for dose selection. Marie Viala, Marie Vinches, +8 authors, Diego Tosi. less Br J Cancer, 2018 Feb 14; 118(5). PMID: 29438365 Free PMC article.
CD8+ T Cells and NK Cells: Parallel and Complementary Soldiers of Immunotherapy. Jillian Rosenberg, Jun Huang. Curr Opin Chem Eng, 2018 Apr 07; 19. PMID: 29623254 Free PMC article.
Complex role of NK cells in regulation of oncolytic virus-bortezomib therapy. Yangjin Kim, Ji Young Yoo, +5 authors, Avner Friedman. less Proc Natl Acad Sci U S A, 2018 Apr 25; 115(19). PMID: 29686060 Free PMC article.
A phase 1 study of lirilumab (antibody against killer immunoglobulin-like receptor antibody KIR2D; IPH2102) in patients with solid tumors and hematologic malignancies. Norbert Vey, Lionel Karlin, +11 authors, Anthony Gonçalves. less Oncotarget, 2018 May 01; 9(25). PMID: 29707140 Free PMC article. Highly Cited.
In situ delivery of allogeneic natural killer cell (NK) combined with Cetuximab in liver metastases of gastrointestinal carcinoma: A phase I clinical trial. O Adotevi, Y Godet, +18 authors, C Borg. less Oncoimmunology, 2018 May 04; 7(5). PMID: 29721386 Free PMC article.
The combination of anti-KIR monoclonal antibodies with anti-PD-1/PD-L1 monoclonal antibodies could be a critical breakthrough in overcoming tumor immune escape in NSCLC. Yayi He, Sangtian Liu, +3 authors, Daniel Chan. less Drug Des Devel Ther, 2018 May 08; 12. PMID: 29731605 Free PMC article.
Immunomodulatory Drugs Exert Anti-Leukemia Effects in Acute Myeloid Leukemia by Direct and Immunostimulatory Activities. Aude Le Roy, Thomas Prébet, +14 authors, Daniel Olive. less Front Immunol, 2018 May 22; 9. PMID: 29780393 Free PMC article.
High-Risk Leukemia: Past, Present, and Future Role of NK Cells. Melissa Mavers, Alice Bertaina. J Immunol Res, 2018 Jun 01; 2018. PMID: 29850617 Free PMC article. Review.
Tumor immunotherapy: New aspects of natural killer cells. Yangxi Li, Rui Sun. Chin J Cancer Res, 2018 Jun 05; 30(2). PMID: 29861604 Free PMC article.
Immunosenescence and Immunotherapy in Elderly Acute Myeloid Leukemia Patients: Time for a Biology-Driven Approach. Alessandro Isidori, Federica Loscocco, +8 authors, Antonio Curti. less Cancers (Basel), 2018 Jun 23; 10(7). PMID: 29932105 Free PMC article. Review.
Expansion of allogeneic NK cells with efficient antibody-dependent cell cytotoxicity against multiple tumors. Diego Sanchez-Martinez, Nerea Allende-Vega, +15 authors, Martin Villalba. less Theranostics, 2018 Aug 08; 8(14). PMID: 30083264 Free PMC article.
Targeting Checkpoint Receptors and Molecules for Therapeutic Modulation of Natural Killer Cells. Nayoung Kim, Hun Sik Kim. Front Immunol, 2018 Sep 27; 9. PMID: 30250471 Free PMC article. Highly Cited. Review.
New miRNA Signature Heralds Human NK Cell Subsets at Different Maturation Steps: Involvement of miR-146a-5p in the Regulation of KIR Expression. Silvia Pesce, Margherita Squillario, +8 authors, Emanuela Marcenaro. less Front Immunol, 2018 Oct 31; 9. PMID: 30374356 Free PMC article.
TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer. Alexandre Ivagnès, Meriem Messaoudene, +23 authors, Laurence Zitvogel. less Oncoimmunology, 2017 Oct 11; 7(12). PMID: 30524877 Free PMC article.
NK Cell-Based Immunotherapy for Hematological Malignancies. Simona Sivori, Raffaella Meazza, +6 authors, Daniela Pende. less J Clin Med, 2019 Oct 19; 8(10). PMID: 31623224 Free PMC article. Review.
The Rise of NK Cell Checkpoints as Promising Therapeutic Targets in Cancer Immunotherapy. Haoyu Sun, Cheng Sun. Front Immunol, 2019 Nov 05; 10. PMID: 31681269 Free PMC article. Review.
Natural Killer Cells in Myeloid Malignancies: Immune Surveillance, NK Cell Dysfunction, and Pharmacological Opportunities to Bolster the Endogenous NK Cells. Mattias Carlsten, Marcus Järås. Front Immunol, 2019 Nov 05; 10. PMID: 31681270 Free PMC article. Review.
Innate Immune Responses in the Outcome of Haploidentical Hematopoietic Stem Cell Transplantation to Cure Hematologic Malignancies. Elisa Zaghi, Michela Calvi, Clara Di Vito, Domenico Mavilio. Front Immunol, 2019 Dec 19; 10. PMID: 31849972 Free PMC article. Review.
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. Review.
Harnessing NK Cells for Cancer Treatment. Paola Minetto, Fabio Guolo, +7 authors, Emanuela Marcenaro. less Front Immunol, 2019 Dec 24; 10. PMID: 31867006 Free PMC article. Review.
A Genetically Engineered Primary Human Natural Killer Cell Platform for Cancer Immunotherapy. Emily J Pomeroy, John T Hunzeker, +13 authors, Branden S Moriarity. less Mol Ther, 2019 Nov 11; 28(1). PMID: 31704085 Free PMC article.
Non-Genetically Improving the Natural Cytotoxicity of Natural Killer (NK) Cells. Martin Villalba, Catherine Alexia, +2 authors, Delphine Gitenay. less Front Immunol, 2020 Jan 31; 10. PMID: 31998309 Free PMC article. Review.
NK Cell-Based Immune Checkpoint Inhibition. Muhammad Khan, Sumbal Arooj, Hua Wang. Front Immunol, 2020 Mar 03; 11. PMID: 32117298 Free PMC article. Review.
Strategies to enhance NK cell function for the treatment of tumors and infections. Jacquelyn Freund-Brown, Leilani Chirino, Taku Kambayashi. Crit Rev Immunol, 2018 Jun 29; 38(2). PMID: 29953390 Free PMC article. Review.
Unleashing Natural Killer Cells in the Tumor Microenvironment-The Next Generation of Immunotherapy? Aviad Ben-Shmuel, Guy Biber, Mira Barda-Saad. Front Immunol, 2020 Mar 11; 11. PMID: 32153582 Free PMC article. Review.
miRNAs in NK Cell-Based Immune Responses and Cancer Immunotherapy. Silvia Pesce, Marco Greppi, +8 authors, Emanuela Marcenaro. less Front Cell Dev Biol, 2020 Mar 13; 8. PMID: 32161759 Free PMC article. Review.
NK Cell-Based Immunotherapy in Renal Cell Carcinoma. Iñigo Terrén, Ane Orrantia, +3 authors, Francisco Borrego. less Cancers (Basel), 2020 Feb 06; 12(2). PMID: 32013092 Free PMC article. Review.
Cancer Immunotherapy Based on Natural Killer Cells: Current Progress and New Opportunities. Weilei Hu, Guosheng Wang, +2 authors, Dongsheng Huang, Meihua Sui, Yibing Xu. less Front Immunol, 2019 Jun 20; 10. PMID: 31214177 Free PMC article. Highly Cited. Review.
Acute myeloid leukemia in the elderly: therapeutic options and choice. Jonathan A Webster, Keith W Pratz. Leuk Lymphoma, 2017 Jun 03; 59(2). PMID: 28573892 Free PMC article. Review.
Innate Immune Cells: A Potential and Promising Cell Population for Treating Osteosarcoma. Zenan Wang, Zhan Wang, +3 authors, Binghao Li, Shengdong Wang, Tao Chen, Zhaoming Ye. less Front Immunol, 2019 Jun 04; 10. PMID: 31156651 Free PMC article. Review.
NK Cell Dysfunction and Checkpoint Immunotherapy. Jiacheng Bi, Zhigang Tian. Front Immunol, 2019 Sep 26; 10. PMID: 31552017 Free PMC article. Review.
Killer immunoglobulin-like receptors/human leukocyte antigen class-I, a crucial immune pathway in cancer. Yi Xu, Lei Wang, +7 authors, Caicun Zhou. less Ann Transl Med, 2020 Apr 21; 8(5). PMID: 32309391 Free PMC article. Review.
PD/1-PD-Ls Checkpoint: Insight on the Potential Role of NK Cells. Silvia Pesce, Marco Greppi, +5 authors, Emanuela Marcenaro. less Front Immunol, 2019 Jun 20; 10. PMID: 31214193 Free PMC article. Highly Cited. Review.
Killers 2.0: NK cell therapies at the forefront of cancer control. Jonathan J Hodgins, Sarwat T Khan, +2 authors, Maria M Park, Rebecca C Auer, Michele Ardolino. less J Clin Invest, 2019 Sep 04; 129(9). PMID: 31478911 Free PMC article. 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. Review.
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. Review.
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. Review.
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. Review.
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. less Cancers (Basel), 2019 Apr 04; 11(4). PMID: 30939820 Free PMC article. Review.
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. less Ann Transl Med, 2019 Apr 26; 7(5). PMID: 31019955 Free PMC article. Review.
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. Review.
Improving the Clinical Application of Natural Killer Cells by Modulating Signals Signal from Target Cells. Monika Holubova, Martin Leba, +3 authors, Daniel Lysak. less 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. Review.
NK cells for cancer immunotherapy. Noriko Shimasaki, Amit Jain, Dario Campana. Nat Rev Drug Discov, 2020 Jan 08; 19(3). PMID: 31907401 Review.
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. Review.
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. Review.
Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors. Nayoung Kim, Dong-Hee Lee, +5 authors, Hun Sik Kim. less BMB Rep, 2020 Dec 11; 54(1). PMID: 33298244 Free PMC article. Review.
Update of early phase clinical trials in cancer immunotherapy. Dae Ho Lee. BMB Rep, 2021 Jan 08; 54(1). PMID: 33407992 Free PMC article. Review.
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. Review.
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. Review.
The Advances and Challenges of NK Cell-Based Cancer Immunotherapy. Synat Kang, Xuefeng Gao, +3 authors, Li Zhang, Erna Yang, Yonghui Li, Li Yu. less Curr Oncol, 2021 Mar 04; 28(2). PMID: 33652996 Free PMC article. Review.
Enhancing a Natural Killer: Modification of NK Cells for Cancer Immunotherapy. Rasa Islam, Aleta Pupovac, +4 authors, Alan Trounson. less Cells, 2021 May 06; 10(5). PMID: 33946954 Free PMC article. Review.
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. less 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. less Cells, 2021 Jul 03; 10(6). PMID: 34203935 Free PMC article. Review.
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. Review.
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. less Int J Mol Sci, 2021 Aug 28; 22(16). PMID: 34445750 Free PMC article. Review.
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. less Int J Mol Sci, 2021 Nov 14; 22(21). PMID: 34768814 Free PMC article. Review.
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. Review.
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. Review.
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. Review.
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. less 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. less 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. less J Transl Med, 2022 May 24; 20(1). PMID: 35606854 Review.
Natural killer cells and acute myeloid leukemia: promises and challenges. Shayan Rahmani, Niloufar Yazdanpanah, Nima Rezaei. Cancer Immunol Immunother, 2022 Jun 01;. PMID: 35639116 Review.

BioKDE: Biomedical Knowledge Discovery Engine

Abstract

Other Links