Horm Metab Res 2008; 40(2): 122-125
DOI: 10.1055/s-2007-1004576
Review

© Georg Thieme Verlag KG Stuttgart · New York

Targeted Cellular Therapy with Natural Killer Cells

H. Klingemann 1 , L. Boissel 1
  • 1Tufts-New England Medical Center and Molecular Oncology Research Institute, Boston, USA
Further Information

Publication History

received 02.08.2007

accepted 27.09.2007

Publication Date:
19 February 2008 (online)

Abstract

Natural killer (NK) cells are believed to be important contributors to a patient's immune armamentarium to fight cancer. However, cancer patients have reportedly defective NK cells and the malignant target frequently has developed mechanisms to escape detection of NK cells. Our research is aimed at overcoming this NK cell paralysis through three different approaches: instead of using autologous NK cells for adoptive immunotherapy, allogeneic NK cells are used that are not inhibited by self histocompatibility antigens. Further, NK cells, selected for a high affinity Fc receptor can, together with monoclonal antibodies, kill targets through ADCC irrespective of any inhibitory receptors. Finally, the genetic engineering of NK cells to express chimeric antigen receptors recognizing antigens on tumor target can overcome inhibitory mechanism and effectively lyse tumor cells.

References

  • 1 Smyth MJ, Hayakawa Y, Takeda K, Yagita H. New aspects of natural killer cell surveillance and therapy.  Nat Rev Cancer. 2002;  2 850-861
  • 2 Arai S, Klingemann HG. Natural killer cells: can they be useful as adoptive immunotherapy for cancer?.  Expert Opin Biol Ther. 2005;  5 163-172
  • 3 Karre K. Express yourself or die: peptides, MHC molecules, and NK cells.  Science. 1995;  267 978-979
  • 4 Lanier LL. Natural killer cells: from no receptors to too many.  Immunity. 1997;  6 371-378
  • 5 Sivori S, Pende D, Bottino C, Marcenaro E, Pessino A, Biassoni R, Moretta L, Moretta A. NKp46 is the major triggering receptor involved in the natural cytotoxicity of fresh or cultured human NK cells. Correlation between surface density of NKp46 and natural cytotoxicity against autologous, allogeneic or xenogeneic target cells.  Eur J Immunol. 1999;  29 1656-1666
  • 6 Iannello A, Ahmad A. Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies.  Cancer Metastasis Rev. 2005;  24 487-499
  • 7 Miller JS, Soignier Y, Panoskaltsis-Mortari A. et al . Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer.  Blood. 2005;  105 3051-3057
  • 8 Gong JH, Maki G, Klingemann HG. Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells.  Leukemia. 1994;  8 652-658
  • 9 Tam YK, Miyagawa B, Ho VC, Klingemann HG. Immunotherapy of malignant melanoma in a SCID mouse model using the highly cytotoxic natural killer cell line NK-92.  J Hematother. 1999;  8 281-290
  • 10 Klingemann HG, Wong E, Maki G. A cytotoxic NK-cell line (NK-92) for ex vivo purging of leukemia from blood.  Biol Blood Marrow Transplant. 1996;  2 68-75
  • 11 Arai S, Kindy K, Swearingen M, Meagher R, Friend P, Maki G, Martinson J, Myint H, Klingemann HG. Phase I study of adoptive immunotherapy using the cytotoxic natural killer (NK) cell line, NK-92, for treatment of advanced renal cell carcinoma and malignant melanoma.  Blood. 2003;  102 693a
  • 12 Tonn T, Becker Sesser R, Schwabe D, Seifired E. Cellular immunotherapy of malignancies using the cloncal natural killer cell line NK-92.  J Hematother Stem Cell Res. 2001;  10 535
  • 13 Moritz D, Wels W, Mattern J, Groner B. Cytotoxic T lymphocytes with a grafted recognition specificity for ERBB2-expressing tumor cells.  Proc Natl Acad Sci USA. 1994;  91 4318-4322
  • 14 Uherek C, Tonn T, Uherek B, Becker S, Schnierle B, Klingemann HG, Wels W. Retargeting of natural killer-cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction.  Blood. 2002;  100 1265-1273
  • 15 Romanski A, Uherek C, Bug G. et al . Re-targeting of an NK cell line (NK-92) with specificity for CD19 efficiently kills human B-precursor leukemic cells.  Blood. 2004;  104 751a
  • 16 Mueller T, Uherek C, Maki G, Chow KU, Klingemann HG, Tonn T, Wels WS. Expression of a CD20 specific chimeric antigen receptor enhances cytotoxic activity of NK cells and overcomes NK-resistance of leukemia and lymphoma cells.  Canc Immunol Immunother. , in press
  • 17 Carton G, Dacheux L, Salles G. et al . Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa.  Blood. 2002;  99 754-758
  • 18 Treon SP, Hansen M, Branagan AR. Polymorphisms in FcγRIIIA (CD 16) receptor expression are associated with clinical response to rituximab in Waldenstrom's Macroglobulinemia.  J Clin Onc. 2005;  23 474-481

Correspondence

H. KlingemannMD, PhD 

Tufts-New England Medical Center

750 Washington Street

Mail 245

Boston

02111 MA

USA

Phone: +1/617/636 25 20

Fax: +1/617/636 31 94

Email: hklingemann@tufts-nemc.org

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