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Human Natural Killer Cell Line

Natural killer (NK) cells are valued for their ability to target and lyse infected cells and cancer cells. NK cells recognize foreign cells and can induce cell death. In addition, NK cell activities can be regulated by multiple activation and inhibitory receptors.

The NK 3.3 cell line developed by SLU researchers has distinct advantages compared to other NK cells lines. Other NK cell lines have significant limitations such as complicated cultivating methods, inability to differentiate healthy and unhealthy cells, and cancerous behavior. SLU’s NK 3.3 cell line overcomes many of these challenges.

Dr. Jacki Kornbluth developed the NK 3.3 human natural killer (NK) cell line in 1981 while at Saint Louis University. In 1982, she first published a description of the cells in the Journal of Immunology (J. Immunol. 129:2831-2837, 1982).

Human NK cells are a small population of circulating lymphocytes. They represent approximately 2-4% of the lymphocytes in the blood, making it difficult to obtain large numbers of purified cells for study. NK 3.3 is an important tool because the cells can be grown in the laboratory providing a constant, ready supply of cells. Moreover, very large numbers of the cells can be obtained. Even more, the cells were derived from a single NK cell from a single healthy individual. As such, every NK 3.3 is identical to the next. Normally, it would be impossible to obtain large numbers of NK cells from a single individual. In addition, not every NK cell from the same individual is identical.

NK 3.3 is the only known “normal” human NK cell line available. There are at least two other human NK cell lines, developed by other investigators, both of which were derived from patients with leukemia. In contrast, NK 3.3 was generated from the blood of a healthy adult male.

Publications and References

Kornbluth J, Flomenberg N, and Dupont B: Cell surface phenotype of a cloned line of human natural killer cells. J. Immunol. 129:2831-2837, 1982.

Kornbluth J and Wilson DB: Monoclonal antibodies directed against HLA molecules affect the lytic and proliferative behavior of a cloned line of human natural killer cells. Human Immunol. 11:239-247, 1984.

Kornbluth J, Spear B, Raab SS, and Wilson DB: Evidence for the role of class I and class II HLA antigens in the lytic function of a cloned line of human natural killer cells. J. Immunol. 134:728-735, 1985.

Kornbluth J: Human natural killer cells and cytotoxic T-lymphocytes require cell surface carbohydrate determinants for lytic function. Cell. Immunol. 95:276-287, 1985.

Taylor DS, Nowell PC, and Kornbluth J: Functional role of HLA class I cell surface molecules in human T lymphocyte activation and proliferation. Proc. Natl. Acad. Sci. USA 83:4446-4450, 1986.

Hart MK, Kornbluth J, Main EK, Spear BT, Taylor DS, and Wilson DB: Lymphocyte function-associated antigen 1 (LFA-1) and natural killer (NK) cell activity: LFA-1 is not necessary for all killer: target cell interactions. Cell. Immunol. 109:306-317, 1987.

Leiden JM, Gottesdiener KM, Quertermous T, Coury L, Bray RA, Gottschalk L, Seidman JG, Strominger JL, Landay AL, and Kornbluth J: T cell receptor gene rearrangement in human natural killer cells: Natural killer activity is not dependent upon the rearrangement and expression of T cell receptor alpha, beta, or gamma genes. Immunogenetics 27:231-238, 1988.

Kornbluth J and Hoover RG: Changes in gene expression associated with IFN-$ and IL-2 induced augmentation of human NK function. J. Immunol. 141:3234-3240, 1988.

Mahle NH, Radcliff G, Sevilla CL, Kornbluth J, and Callewaert D: Kinetics of cellular cytotoxicity mediated by a cloned human killer cell line. Immunobiol. 179:230-243, 1989.

Kornbluth J and Hoover R: Changes in gene expression associated with natural killer function. In: Natural Killer Cells and Host Defense. E.W. Ades and C. Lopez, eds., S. Karger AG, Basel, p. 68-74, 1989.

Kornbluth J and Hoover RG: Anti-HLA class I antibodies alter gene expression in human natural killer cells. In: Immunobiology of HLA, Vol. 2, Immunogenetics and Histocompatibility, B. Dupont, ed., Springer-Verlag, New York, NY, p. 150-152, 1989.

Kornbluth J, and Searfoss L: C-myb protooncogene levels correlate with interleukin-2 and interferon-$ induced augmentation of natural killer activity. Natural Killer Cells: Biology and Clinical Applications. S. Karger AG, Basel, p. 212-215, 1990.

Hayakawa K, Salmeron MA, Kornbluth J, Bucana C, and Itoh K: The role of IL-4 in proliferation and differentiation of human natural killer cells. Study of an IL-4 dependent versus an IL-2 dependent natural killer cell clone. J. Immunol. 146:2453-2460, 1991.

Chehimi J, Bandyopadhyay B, Prakash K, Perussia B, Hassan NK, Kawashima H, Campbell D, Kornbluth J, and Starr SE: In vitro infection of natural killer cells with different human immunodeficiency virus type 1 isolates. J. Virology. 65:1812-1822, 1991.

Kozlowski M, Schorey J, Portis T, Grigoriev V and Kornbluth J: NKLAM: A novel gene selectively expressed in cells with cytolytic function. J. Immunol.163:1775-1785, 1999.

Portis T, Anderson J, Esposito A and Kornbluth J: Gene structure of human and murine NKLAM, a gene associated with cellular cytotoxicity. Immunogenetics 51:546-555, 2000.

Fortier J and Kornbluth J: NK Lytic-Associated Molecule, involved in NK cytolytic function, is an E3 ligase. J. Immunol. 176: 6454-6463, 2006.

Hoover RG, Gullickson G and Kornbluth J: Impaired NK cytolytic activity and enhanced tumor growth in NK Lytic- Associated Molecule (NKLAM)-deficient mice. J. Immunol. 183: 6913-69211, 2009.

Lawrence DW and Kornbluth J: E3 ubiquitin ligase NKLAM is a macrophage phagosome protein and plays a role in bacterial killing. Cell. Immunol. 279: 46-52, 2012.

Hoover RG, Gullickson G and Kornbluth J: Natural killer lytic-associated molecule plays a role in controlling tumor dissemination and metastasis. Frontiers Immunol. 3 (393): 1-9, 2012.

Bhattacharya S, Muhammad N, Steele R, Kornbluth J, Ray RB: Bitter melon enhances natural killer-mediated toxicity against head and neck cancer cells. Cancer Prev. Res. 10 (6):1-7, 2017.

 
 
Benefits
 

The advantages of SLU’s NK 3.3 cell line include:

  • Identical cells derived from a single cell from a single healthy human male.
  • Looks and acts the same as NK cells isolated from adult blood.
  • Activity can be regulated by the same factors that regulate normal NK cells.
  • Receptive to medium scale laboratory production.
  • Relatively simple cultivating method that requires minimal maintenance.
  • Requires only basic cultures and supplements for cultivation.
  • Possesses both innate and adaptive immunity.
  • Cell surface expression of CD16, which enables the use of antibody-dependent cell-mediated cytotoxicity
  • (ADCC) and is not found in other NK cell lines.
 
 
Applications
 

The NK 3.3 cell line is useful for life sciences research including cancer and viral immunotherapy. Numerous top ranked life sciences, bio‑technology, and bio‑pharmaceutical companies have licensed the NK 3.3 cell line over the years. This cell line has been used by multiple investigators throughout the world.

Additional Details

Owner

University of St. Louis

Intellectual Property Protection

Pending Patent



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