Cancer Immunology, Immunotherapy

, Volume 65, Issue 4, pp 485–492 | Cite as

NK-92: an ‘off-the-shelf therapeutic’ for adoptive natural killer cell-based cancer immunotherapy

  • Garnet Suck
  • Marcus Odendahl
  • Paulina Nowakowska
  • Christian Seidl
  • Winfried S. Wels
  • Hans G. Klingemann
  • Torsten Tonn
Symposium-in-writing paper

Abstract

Natural killer (NK) cells are increasingly considered as immunotherapeutic agents in particular in the fight against cancers. NK cell therapies are potentially broadly applicable and, different from their T cell counterparts, do not cause graft-versus-host disease. Efficacy and clinical in vitro or in vivo expansion of primary NK cells will however always remain variable due to individual differences of donors or patients. Long-term storage of clinical NK cell lots to allow repeated clinical applications remains an additional challenge. In contrast, the established and well-characterized cell line NK-92 can be easily and reproducibly expanded from a good manufacturing practice (GMP)-compliant cryopreserved master cell bank. Moreover, no cost-intensive cell purification methods are required. To date, NK-92 has been intensively studied. The cells displayed superior cytotoxicity against a number of tumor types tested, which was confirmed in preclinical mouse studies. Subsequent clinical testing demonstrated safety of NK-92 infusions even at high doses. Despite the phase I nature of the trials conducted so far, some efficacy was noted, particularly against lung tumors. Furthermore, to overcome tumor resistance and for specific targeting, NK-92 has been engineered to express a number of different chimeric antigen receptors (CARs), including targeting, for example, CD19 or CD20 (anti-B cell malignancies), CD38 (anti-myeloma) or human epidermal growth factor receptor 2 (HER2; ErbB2; anti-epithelial cancers). The concept of an NK cell line as an allogeneic cell therapeutic produced ‘off-the-shelf’ on demand holds great promise for the development of effective treatments.

Keywords

NK-92 Cellular immunotherapy CAR Clinical trial NK cell line Tumor targeting 

Abbreviations

ADCC

Antibody-dependent cell-mediated cytotoxicity

ALL

Acute lymphoblastic leukemia

BIKE or TRIKE

Bi-specific or tri-specific killer engager

CAR

Chimeric antigen receptor

CLL

Chronic lymphocytic leukemia

EBV

Epstein–Barr virus

EPCAM

Epithelial cell adhesion molecule

E:T

Effector:target

Fc

Fragment crystallizable region

GMP

Good manufacturing practice

GvHD

Graft-versus-host disease

HER2; ErbB2

Human epidermal growth factor receptor 2

HLA

Human leukocyte antigen

IgG

Immunoglobulin G

IL

Interleukin

KIR

Killer cell immunoglobulin-like receptor

LIR-1

Leukocyte immunoglobulin-like receptor

MICA

MHC class I chain-related gene A

MICB

MHC class I chain-related gene B

NK

Natural killer

NKG

Natural killer group

PBMC

Peripheral blood mononuclear cell

RCC

Renal cell carcinoma

RECIST

Response Evaluation Criteria in Solid Tumors

scFv

Single-chain variable fragment

SCID

Severe combined immunodeficiency

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Garnet Suck
    • 1
  • Marcus Odendahl
    • 2
  • Paulina Nowakowska
    • 3
  • Christian Seidl
    • 3
  • Winfried S. Wels
    • 4
  • Hans G. Klingemann
    • 5
  • Torsten Tonn
    • 2
    • 3
    • 6
  1. 1.Institute for Transfusion MedicineGerman Red Cross Blood Donation Service North-EastBerlinGermany
  2. 2.Institute for Transfusion MedicineGerman Red Cross Blood Donation Service North-EastDresdenGermany
  3. 3.Institute for Transfusion Medicine and ImmunohematologyGerman Red Cross Blood Donation Service Baden-Württemberg-HessenFrankfurt am MainGermany
  4. 4.Institute for Tumor Biology and Experimental TherapyGeorg-Speyer-HausFrankfurt am MainGermany
  5. 5.NantKwest IncCulver CityUSA
  6. 6.Medical Faculty Carl Gustav CarusTechnische Universität DresdenDresdenGermany

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