본문 바로가기
KERD
논문KCI 등재

Expansion and Activation of Natural Killer Cells for Cancer Immunotherapy

조덕|Dario Campana
대한진단검사의학회 (Korean Society For Laboratory Medicine)|2009.04|Annals of Laboratory Medicine|제29권 제2호|pp. 89-96

2

조회

0

다운로드

7

인용

0

참고문헌

키워드

NK cellsAcute lymphoblastic leukemiaAcute myeloid leukemiaCell therapyChimeric receptors
주제분류병리학

초록

Natural killer (NK) cells can kill a wide range of cancer cells and are a promising tool for cell therapy of cancer. NK cells cytotoxicity is regulated by a balance between stimulatory and inhibitory signals. Interleukin-2 is known to increase NK cell cytotoxicity. Although many cytokines have been studied in efforts to induce durable NK cell expansions, most reports indicate a rather modest effect and the requirement for additional stimuli. We found that contact with the K562 myeloid leukemia cell line, genetically modified to express a membrane-bound form of interleukin-15 and the ligand for the costimulatory molecule 4-1BB, induced vigorous expansion of NK cells from peripheral blood. Based on these findings, we developed a method for large-scale clinical-grade expansion of NK cells. This method is currently used to expand allogeneic NK cells for infusion in patients with leukemia and solid tumors. We here summarize methods for expansion and activation of NK cells from human peripheral blood mononuclear cells as well as clinical-scale methods to produce NK cells for immunotherapy under Current Good Manufacturing Practices (cGMP) conditions.

Abstract

Natural killer (NK) cells can kill a wide range of cancer cells and are a promising tool for cell therapy of cancer. NK cells cytotoxicity is regulated by a balance between stimulatory and inhibitory signals. Interleukin-2 is known to increase NK cell cytotoxicity. Although many cytokines have been studied in efforts to induce durable NK cell expansions, most reports indicate a rather modest effect and the requirement for additional stimuli. We found that contact with the K562 myeloid leukemia cell line, genetically modified to express a membrane-bound form of interleukin-15 and the ligand for the costimulatory molecule 4-1BB, induced vigorous expansion of NK cells from peripheral blood. Based on these findings, we developed a method for large-scale clinical-grade expansion of NK cells. This method is currently used to expand allogeneic NK cells for infusion in patients with leukemia and solid tumors. We here summarize methods for expansion and activation of NK cells from human peripheral blood mononuclear cells as well as clinical-scale methods to produce NK cells for immunotherapy under Current Good Manufacturing Practices (cGMP) conditions.

참고문헌 (62)

  1. Galy A, "Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset", Immunity, 3, pp.459~473 (1995)
  2. Farag SS, "Human natural killer cell development and biology", Blood Rev, 20, pp.123~137 (2006)
  3. Lanier LL, "NK cell recognition", Annu Rev Immunol, 23, pp.225~274 (2005)
  4. Caligiuri MA, "Human natural killer cells", Blood, 112, pp.461~469 (2008)
  5. Cooper MA, "The biology of human natural killer-cell subsets", Trends Immunol, 22, pp.633~640 (2001)
  6. Fehniger TA, "CD56 bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity", Blood, 101, pp.3052~3057 (2003)
  7. Lundqvist A, "Bortezomib and depsipeptide sensitize tumors to tumor necrosis factor-related apoptosis-inducing ligand: a novel method to potentiate natural killer cell tumor cytotoxicity", Cancer Res, 66, pp.7317~7325 (2006)
  8. Srivastava S, "Natural killer cell immuno-therapy for cancer: a new hope", Cytotherapy, 10, pp.775~783 (2008)
  9. Moretta L, "Unravelling natural killer cell function:triggering and inhibitory human NK receptors", EMBO J, 23, pp.255~259 (2004)
  10. Lanier LL, "Up on the tightrope: natural killer cell activation and inhibition", Nat Immunol, 9, pp.495~502 (2008)
  11. Ljunggren HG, "In search of the 'missing self': MHC molecules and NK cell recognition", Immunol Today, 11, pp.237~244 (1990)
  12. Yokoyama WM, "Licensing of natural killer cells by selfmajor histocompatibility complex class Ⅰ", Immunol Rev, 214, pp.143~154 (2006)
  13. Terme M, "Natural killer cell-directed therapies: moving from unexpected results to successful strategies", Nat Immunol, 9, pp.486~494 (2008)
  14. Trinchieri G, "Response of resting human peripheral blood natural killer cells to interleukin 2", J Exp Med, 160, pp.1147~1169 (1984)
  15. Phillips JH, "Dissection of the lymphokine-activated killer phenomenon. Relative contribution of peripheral blood natural killer cells and T lymphocytes to cytolysis", J Exp Med, 164, pp.814~825 (1986)
  16. London L, "Induction of proliferation in vitro of resting human natural killer cells: IL 2 induces into cell cycle most peripheral blood NK cells, but only a minor subset of low density T cells", J Immunol, 137, pp.3845~3854 (1986)
  17. Lanier LL, "Interleukin 2 activation of natural killer cells rapidly induces the expression and phosphorylation of the Leu-23 activation antigen", J Exp Med, 167, pp.1572~1585 (1988)
  18. Robertson MJ, "Costimulatory signals are required for optimal proliferation of human natural killer cells", J Immunol, 150, pp.1705~1714 (1993)
  19. Imai C, "Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells", Blood, 106, pp.376~383 (2005)
  20. Alici E, "Autologous antitumor activity by NK cells expanded from myeloma patients using GMP-compliant components", Blood, 111, pp.3155~3162 (2008)
  21. Carlens S, "A new method for in vitro expansion of cytotoxic human CD3-CD56+ natural killer cells", Hum Immunol, 62, pp.1092~1098
  22. Rosenberg SA, "Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer", N Engl J Med, 313, pp.1485~1492 (1985)
  23. Miller JS, "Role of monocytes in the expansion of human activated natural killer cells", Blood, 80, pp.2221~2229 (1992)
  24. Robertson MJ, "Costimulation of human natural killer cell proliferation: role of accessory cytokines and cell contact-dependent signals", Nat Immun, 15, pp.213~226 (1996)
  25. Rabinowich H, "Increased proliferation, lytic activity, and purity of human natural killer cells cocultured with mitogen-activated feeder cells", Cell Immunol, 135, pp.454~470 (1991)
  26. Igarashi T, "Enhanced cytotoxicity of allogeneic NK cells with killer immunoglobulin-like receptor ligand incompatibility against melanoma and renal cell carcinoma cells", Blood, 104, pp.170~177 (2004)
  27. Perussia B, "Preferential proliferation of natural killer cells among peripheral blood mononuclear cells cocultured with B lymphoblastoid cell lines", Nat Immun Cell Growth Regul, 6, pp.171~188 (1987)
  28. Harada H, "Selective expansion of human natural killer cells from peripheral blood mononuclear cells by the cell line, HFWT", Jpn J Cancer Res, 93, pp.313~319 (2002)
  29. Luhm J, "Large-scale generation of natural killer lymphocytes for clinical application", J Hematother Stem Cell Res, 11, pp.651~657 (2002)
  30. Condiotti R, "Ex vivo expansion of CD56+ cytotoxic cells from human umbilical cord blood", Exp Hematol, 29, pp.104~113 (2001)
  31. Boissel L, "Umbilical cord mesenchymal stem cells increase expansion of cord blood natural killer cells", Biol Blood Marrow Transplant, 14, pp.1031~1038 (2008)
  32. Phillips JH, "A model for the differentiation of human natural killer cells. Studies on the in vitro activation of Leu-11+ gran-ular lymphocytes with a natural killer-sensitive tumor cell, K562", J Exp Med, 161, pp.1464~1482 (1985)
  33. Melero I, "NK1.1 cells express 4-1BB (CDw137) costimulatory molecule and are required for tumor immunity elicited by anti-4-1BB monoclonal antibodies", Cell Immunol, 190, pp.167~172 (1998)
  34. Carson WE, "A potential role for interleukin-15 in the regulation of human natural killer cell survival", J Clin Invest, 99, pp.937~943 (1997)
  35. Cooper MA, "In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells", Blood, 100, pp.3633~3638 (2002)
  36. Fehniger TA, "Ontogeny and expansion of human natural killer cells: clinical implications", Int Rev Immunol, 20, pp.503~534 (2001)
  37. Wu J, "Natural killer cells and cancer", Adv Cancer Res, 90, pp.127~156 (2003)
  38. Musso T, "Human monocytes constitutively express membrane-bound, biologically active, and interferon-gamma-upregulated interleukin-15", Blood, 93, pp.3531~3539 (1999)
  39. Dubois S, "IL-15Ralpha recycles and presents IL-15 In trans to neighboring cells", Immunity, 17, pp.537~547 (2002)
  40. Koka R, "Cutting edge: murine dendritic cells require IL-15R alpha to prime NK cells", J Immunol, 173, pp.3594~3598 (2004)
  41. Burkett PR, "Coordinate expression and trans presentation of interleukin (IL)-15Ralpha and IL-15 supports natural killer cell and memory CD8+ T cell homeostasis", J Exp Med, 200, pp.825~834 (2004)
  42. Kobayashi H, "Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance", Blood, 105, pp.721~727 (2005)
  43. Fujisaki H, "Expansion of highly cytotoxic human natural killer cells for cancer cell therapy", Cancer Res (2009)
  44. Leung W, "Phenotype and function of human natural killer cells purified by using a clinical-scale immunomagnetic method", Cancer Immunol Immunother, 54, pp.389~394 (2005)
  45. Meehan KR, "Development of a clinical model for ex vivo expansion of multiple populations of effector cells for adoptive cellular therapy", Cytotherapy, 10, pp.30~37 (2008)
  46. Miller JS, "Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer", Blood, 105, pp.3051~3057 (2005)
  47. Klingemann HG, "Ex vivo expansion of natural killer cells for clinical applica", Cytotherapy, 6, pp.15~22 (2004)
  48. McKenna DH Jr, "Good manufacturing practices production of natural killer cells for immunotherapy: a six-year single-institution experience", Transfusion, 47, pp.520~528 (2007)
  49. Torelli GF, "Expansion of natural killer cells with lytic activity against autologous blasts from adult and pediatric acute lymphoid leukemia patients in complete hematologic remission", Haematologica, 90, pp.785~792 (2005)
  50. Tam YK, "Ex vivo expansion of the highly cytotoxic human natural killer-92 cell-line under current good manufacturing practice conditions for clinical adoptive cellular immunotherapy", Cytotherapy, 5, pp.259~272 (2003)
  51. Ruggeri L, "Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants", Science, 295, pp.2097~2100 (2002)
  52. Ruggeri L, "Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation", Blood, 94, pp.333~339 (1999)
  53. Giebel S, "Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors", Blood, 102, pp.814~819 (2003)
  54. Leung W, "Determinants of antileukemia effects of allogeneic NK cells", J Immunol, 172, pp.644~650 (2004)
  55. Rooney CM, "Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients", Blood, 92, pp.1549~1555 (1998)
  56. Wagner HJ, "A strategy for treatment of Epstein-Barr virus-positive Hodgkin's disease by targeting interleukin 12 to the tumor environment using tumor antigen-specific T cells", Cancer Gene Ther, 11, pp.81~91 (2004)
  57. Comoli P, "Adoptive transfer of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T cells with in vitro antitumor activity boosts LMP2-specific immune response in a patient with EBV-related nasopharyngeal carcinoma", Ann Oncol, 15, pp.113~117 (2004)
  58. Klein G, "Surveillance against tumors--is it mainly immunological?", Immunol Lett, 100, pp.29~33 (2005)
  59. Main EK, "Human neuroblastoma cell lines are susceptible to lysis by natural killer cells but not by cytotoxic T lymphocytes", J Immunol, 135, pp.242~246 (1985)
  60. Raffaghello L, "Mechanisms of immune evasion of human neuroblastoma", Cancer Letters, 228, pp.155~161 (2005)
  61. Sadelain M, "Targeting tumours with genetically enhanced T lymphocytes", Nat Rev Cancer, 3, pp.35~45 (2003)
  62. Imai C, "Genetic modification of T cells for cancer therapy", J Biol Regul Homeost Agents, 18, pp.62~71 (2004)

관련 논문AI추천

Optimization of Large-Scale Expansion and Cryopreservation of Human Natural Killer Cells for Anti-Tumor Therapy김효진, 민보경, 신의철, 이은경, 정미영, 조성유, 최하나, 허정현, 황유경대한면역학회 · Immune Network2018 · 제18권 제4호Cytokines in Focus: IL-2 and IL-15 in NK Adoptive Cell Cancer Immunotherapy장미희, Bryan Marr, Donghyeon Jo, Seung-Hwan Lee대한면역학회 · Immune Network2025 · 제25권 제2호NK Cell-Based Immunotherapies in Cancer김성진, 신민화, 이경미, Junghee Kim, Jungwon Kim, Siyoung A. Lim대한면역학회 · Immune Network2020 · 제20권 제2호Feeder-Free Expanded and Cryopreserved NK Cells Retain Antibody-Dependent Cell Cytotoxicity against HER2-Positive TumorsBaek Youngseok, Jin Chaeyeon, Kim Suwoo, Kwack KyuBum, Lee Injee한국미생물·생명공학회 · Journal of Microbiology and Biotechnology2025 · 제35권 Natural Killer Cell Expansion and Cytotoxicity Differ Depending on the Culture Medium Used신수, 김성은, Ahn Yong-Oon, Cho Duck, Doh Junsang, Hwang Ilwoong, Kim Jinho, Koh Seung Kwon, Lim Yuree, Park Jeehun, Phan Minh-Trang Thi대한진단검사의학회 · Annals of Laboratory Medicine2022 · 제42권 제6호Ex Vivo Expansion of Highly Cytotoxic Natural Killer Cells Using Optimal Culture Medium김석호대한진단검사의학회 · Annals of Laboratory Medicine2022 · 제42권 제6호

이 간행물의 다른 논문 (13건)

B형 Niemann-Pick 병에 이환된 한국인 성인 1예: 이차성 Sea-blue 조직구증 및 분자적 특성 규명유한욱, 김구환, 박찬정, 이원미, 우정주, 채정돈, 조영욱, 공수정, 이홍복pp. 97-103The Comparison of Parathyroid Hormone Degradation Effect by Various Protease Inhibitors in Blood Specimen김영식, 이혜경, 권희정pp. 104-109임신성 당뇨병 선별검사 시점 및 HbA1c 농도와 신생아의 예후와의 관계이원배, 빈중현, 성인경, 강지민, 전정식, 이현승, 이정현, 김소영, 최윤정pp. 110-115쯔쯔가무시 환자의 단클론성 및 이클론성 감마글로불린병증 빈도 및 유형조지현, 박도심pp. 116-121Clostridium difficile 독소 A 및 독소 B 검출을 위한 효소면역법의 비교유수진, 신보문, 오혜전pp. 122-126
원문 보기