Skip to main content
SpringerLink
Log in

NK-92 Cytotoxicity Against Cancer Stem Cells in Hematologic Malignancies

  • Chapter
  • First Online:
Stem Cells and Cancer Stem Cells, Volume 9

Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 9))

Abstract

The discovery that many cancers are driven by a rare population of cancer stem cells has raised new questions as to how the immune system recognizes these cells. There is evidence to support an immunophenotypically defined stem cell in acute myeloid leukemia and multiple myeloma, two common hematologic malignancies. While chemotherapy can cure a minority of AML patients, multiple myeloma is generally incurable with this approach. However, allogeneic stem cell transplantation is the most effective therapy for AML implying an important role for the graft-versus-leukemia effect while multiple myeloma is typically treated with autologous bone marrow transplantation. One novel emerging therapeutic approach is the use of immune effector cell lines that have a broad tumour killing capacity such as NK-92. Here we review the role of NK-92 in the recognition and killing of cancer stem cells in leukemia and multiple myeloma and outline the application of clonogenic cytotoxicity assays to study these immunologic interactions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Arai S, Meagher R, Swearingen M, Myint H, Rich E, Martinson J, Klingemann H (2008) Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial. Cytotherapy 10(6):625–632

    Article  PubMed  CAS  Google Scholar 

  • Arora M, Weisdorf DJ, Spellman SR, Haagenson MD, Klein JP, Hurley CK, Selby GB, Antin JH, Kernan NA, Kollman C, Nademanee A, McGlave P, Horowitz MM, Petersdorf EW (2009) HLA-identical sibling compared with 8/8 matched and mismatched unrelated donor bone marrow transplant for chronic phase chronic myeloid leukemia. J Clin Oncol 27(10):1644–1652

    Article  PubMed  Google Scholar 

  • Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3(7):730–737

    Article  PubMed  CAS  Google Scholar 

  • Bradley TR, Metcalf D (1966) The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci 44(3):287–299

    Article  PubMed  CAS  Google Scholar 

  • Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, Giaccone L, Sorasio R, Omede P, Baldi I, Bringhen S, Massaia M, Aglietta M, Levis A, Gallamini A, Fanin R, Palumbo A, Storb R, Ciccone G, Boccadoro M (2009) A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med 356(11):1110–1120

    Article  Google Scholar 

  • Burke MJ, Cao Q, Trotz B, Weigel B, Kumar A, Smith A, Verneris MR (2009) Allogeneic hematopoietic cell transplantation (allogeneic HCT) for treatment of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). Pediatr Blood Cancer 53(7):1289–1294

    Article  PubMed  Google Scholar 

  • Cesano A, Santoli D (1992) Two unique human leukemic T-cell lines endowed with a stable cytotoxic function and a different spectrum of target reactivity analysis and modulation of their lytic mechanisms. In Vitro Cell Dev Biol 28A(9–10):648–656

    Article  PubMed  CAS  Google Scholar 

  • Cieciura SJ, Marcus PI, Puck TT (1956) Clonal growth in vitro of epithelial cells from normal human tissues. J Exp Med 104(4):615–628

    Article  PubMed  CAS  Google Scholar 

  • Costello RT, Mallet F, Gaugler B, Sainty D, Arnoulet C, Gastaut JA, Olive D (2000) Human acute myeloid leukemia CD34+/CD38− progenitor cells have decreased sensitivity to chemotherapy and Fas-induced apoptosis, reduced immunogenicity, and impaired dendritic cell transformation capacities. Cancer Res 60(16):4403–4411

    PubMed  CAS  Google Scholar 

  • Diermayr S, Himmelreich H, Durovic B, Mathys-Schneeberger A, Siegler U, Langenkamp U, Hofsteenge J, Gratwohl A, Tichelli A, Paluszewska M, Wiktor-Jedrzejczak W, Kalberer CP, Wodnar-Filipowicz A (2008) NKG2D ligand expression in AML increases in response to HDAC inhibitor valproic acid and contributes to allorecognition by NK-cell lines with single KIR-HLA class I specificities. Blood 111(3):1428–1436

    Article  PubMed  CAS  Google Scholar 

  • Gong JH, Maki G, Klingemann HG (1994) Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. Leukemia 8(4):652

    PubMed  CAS  Google Scholar 

  • Hoffman RM (1991) In vitro sensitivity assays in cancer: a review, analysis, and prognosis. J Clin Lab Anal 5(2):133–143

    Article  PubMed  CAS  Google Scholar 

  • Hurwitz CA, Mounce KG, Grier HE (1995) Treatment of patients with acute myelogenous leukemia: review of clinical trials of the past decade. J Pediatr Hematol Oncol 17(3):185–197

    Article  PubMed  CAS  Google Scholar 

  • Karre K, Ljunggren HG, Piontek G, Kiessling R (1986) Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319(6055):675–678

    Article  PubMed  CAS  Google Scholar 

  • Langenkamp U, Siegler U, Jorger S, Diermayr S, Gratwohl A, Kalberer CP, Wodnar-Filipowicz A (2009) Human acute myeloid leukemia CD34  +  CD38− stem cells are susceptible to allorecognition and lysis by single KIR-expressing natural killer cells. Haematologica 94(11):1590–1594

    Article  PubMed  Google Scholar 

  • Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367(6464):645–648

    Article  PubMed  CAS  Google Scholar 

  • Litzow MR, Tarima S, Perez WS, Bolwell BJ, Cairo MS, Camitta BM, Cutler CS, de Lima M, Dipersio JF, Gale RP, Keating A, Lazarus HM, Luger S, Marks DI, Maziarz RT, McCarthy PL, Pasquini MC, Phillips GL, Rizzo JD, Sierra J, Tallman MS, Weisdorf DJ (2010) Allogeneic transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia. Blood 115(9):1850–1857

    Article  PubMed  CAS  Google Scholar 

  • Lowenberg B, Downing JR, Burnett A (1999) Acute myeloid leukemia. N Engl J Med 341(14):1051–1062

    Article  PubMed  CAS  Google Scholar 

  • Matsui W, Wang Q, Barber JP, Brennan S, Smith BD, Borrello I, McNiece I, Lin L, Ambinder RF, Peacock C, Watkins DN, Huff CA, Jones RJ (2008) Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res 68(1):190–197

    Article  PubMed  CAS  Google Scholar 

  • McCulloch EA, Till JE (1960) The radiation sensitivity of normal mouse bone marrow cells, determined by quantitative marrow transplantation into irradiated mice. Radiat Res 13:115–125

    Article  PubMed  CAS  Google Scholar 

  • Noonan K, Matsui W, Serafini P, Carbley R, Tan G, Khalili J, Bonyhadi M, Levitsky H, Whartenby K, Borrello I (2005) Activated marrow-infiltrating lymphocytes effectively target plasma cells and their clonogenic precursors. Cancer Res 65(5):2026–2034

    Article  PubMed  CAS  Google Scholar 

  • Ogawa M, Bergsagel DE, McCulloch EA (1973) Sensitivity of human and murine hemopoietic precursor cells to chemotherapeutic agents assessed in cell culture. Blood 42(6):851–856

    PubMed  CAS  Google Scholar 

  • Palumbo A, Anderson K (2011) Multiple myeloma. N Engl J Med 364(11):1046–1060

    Article  PubMed  CAS  Google Scholar 

  • Palumbo A, Rajkumar SV (2009) Treatment of newly diagnosed myeloma. Leukemia 23(3):449–456

    Article  PubMed  CAS  Google Scholar 

  • Park CH, Bergsagel DE, McCulloch EA (1971) Mouse myeloma tumor stem cells: a primary cell culture assay. J Natl Cancer Inst 46(2):411–422

    PubMed  CAS  Google Scholar 

  • Park CH, Amare M, Savin MA, Goodwin JW, Newcomb MM, Hoogstraten B (1980) Prediction of chemotherapy response in human leukemia using an in vitro chemotherapy sensitivity test on the leukemic colony-forming cells. Blood 55(4):595–601

    PubMed  CAS  Google Scholar 

  • Pierce RA, Field ED, Mutis T, Golovina TN, Von Kap-Herr C, Wilke M, Pool J, Shabanowitz J, Pettenati MJ, Eisenlohr LC, Hunt DF, Goulmy E, Engelhard VH (2001) The HA-2 minor histocompatibility antigen is derived from a diallelic gene encoding a novel human class I myosin protein. J Immunol 167(6):3223–3230

    PubMed  CAS  Google Scholar 

  • Puck TT, Marcus PI, Cieciura SJ (1956) Clonal growth of mammalian cells in vitro; growth characteristics of colonies from single HeLa cells with and without a feeder layer. J Exp Med 103(2):273–283

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro RC, Razzouk BI, Pounds S, Hijiya N, Pui CH, Rubnitz JE (2005) Successive clinical trials for childhood acute myeloid leukemia at St Jude Children’s research hospital, from 1980 to 2000. Leukemia 19(12):2125–2129

    Article  PubMed  CAS  Google Scholar 

  • Ries LAG, Krapcho M, Stinchcomb DG, Howlader N, Horner MJ, Mariotto A, Miller BA, Feuer EJ, Altekruse SF, Lewis DR, Clegg L, Eisner MP, Reichman M, Edwards BK (eds) (2008) SEER cancer statistics review, 1975–2005. National Cancer Institute, Bethesda

    Google Scholar 

  • Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F, Martelli MF, Velardi A (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295(5562):2097–2100

    Article  PubMed  CAS  Google Scholar 

  • Sutlu T, Alici E (2009) Natural killer cell-based immunotherapy in cancer: current insights and future prospects. J Intern Med 266(2):154–181

    Article  PubMed  CAS  Google Scholar 

  • Swann JB, Smyth MJ (2007) Immune surveillance of tumors. J Clin Invest 117(5):1137–1146

    Article  PubMed  CAS  Google Scholar 

  • Swift BE, Williams BA, Kosaka Y, Wang XH, Medin JA, Viswanathan S, Martinez-Lopez J, Keating A (2012) Natural killer cell lines preferentially kill clonogenic multiple myeloma cells and decrease myeloma engraftment in a bioluminescent xenograft mouse model. Haematologica 97(7):1020–1028

    Article  PubMed  Google Scholar 

  • Takahashi T, Lim B, Jamal N, Tritchler D, Lockwood G, McKinney S, Bergsagel DE, Messner HA (1985) Colony growth and self renewal of plasma cell precursors in multiple myeloma. J Clin Oncol 3(12):1613–1623

    PubMed  CAS  Google Scholar 

  • Tonn T, Becker S, Esser R, Schwabe D, Seifried E (2001) Cellular immunotherapy of malignancies using the clonal natural killer cell line NK-92. J Hematother Stem Cell Res 10(4):535–544

    Article  PubMed  CAS  Google Scholar 

  • Visonneau S, Cesano A, Porter DL, Luger SL, Schuchter L, Kamoun M, Torosian MH, Duffy K, Sickles C, Stadtmauer EA, Santoli D (2000) Phase I trial of TALL-104 cells in patients with refractory metastatic breast cancer. Clin Cancer Res 6(5):1744–1754

    PubMed  CAS  Google Scholar 

  • Williams BA, Wang XH, Keating A (2010) Clonogenic assays measure leukemia stem cell killing not detectable by chromium release and flow cytometric ­cytotoxicity assays. Cytotherapy 12(7):951–960

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cell Therapy Program, 4-605 Princess Margaret Hospital, 610 University Avenue, Toronto, ON, M5G 2 M9, Canada

    Brent A. Williams, Brenna E. Swift, Richard Cheng & Armand Keating

Authors
  1. Brent A. Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brenna E. Swift
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Armand Keating
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brent A. Williams .

Editor information

Editors and Affiliations

  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Williams, B.A., Swift, B.E., Cheng, R., Keating, A. (2013). NK-92 Cytotoxicity Against Cancer Stem Cells in Hematologic Malignancies. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 9. Stem Cells and Cancer Stem Cells, vol 9. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5645-8_24

Download citation

Publish with us

Policies and ethics

Search

Navigation