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Lymphokine-activated killer cell

Lymphokine-activated killer cell

In cell biology, a lymphokine-activated killer cell (also known as a LAK cell) is a white blood cell, consisting mostly of natural killer, natural killer T, and T cells that has been stimulated to kill tumor cells, but because of the function in which they activate, and the cells they can successfully target, they are classified as different than the classical natural killer and T lymphocyte systems.

Mechanism

It has been shown that when Peripheral blood leukocytes (PBL) are cultured in the presence of Interleukin 2, it results in the development of effector cells, which are cytotoxic and are seen to localize to tumor sites and are capable of lysing fresh, non-cultured cancer cells, both primary and metastatic.[1] LAK cells respond to these lymphokines, particularly IL-2, by developing into effector cells capable of lysing tumor cells that are known to be resistant to NK cell activity. After stimulated by IL-2, LAK cells can target and kill tumor cells in the early innate response.[2]

The mechanism of LAK cells is distinctive from that of natural killer cells because they can lyse cells that NK cells cannot. LAK cells are also capable of acting against cells that do not display the major histocompatibility complex, as has been shown by the ability to cause lysis in non-immunogenic, allogeneic and syngeneic tumors. LAK cells function in the same way as NK cells in the peripheral blood but are more sensitive to and can target tumor cells.

Cancer Treatment

The use of lymphokine activated killer cells has been found to be helpful in treating human cells with different cancers in vitro[3]. LAK cell therapy is a method that uses interleukin 2 (IL-2) to enhance the number of lymphocytes in an in vitro setting, and it has formed the foundation of many immunotherapy assays that are now in use.[4] LAK cells have shown potential as a cellular agent for cancer therapy and have been utilized therapeutically in association with IL-2 for the treatment of various cancers. LAK cells have anticancer efficacy against homologous carcinoma cells and can grow ex vivo in the presence of IL-2.[5] In melanoma and gastric cancer cells, intercellular adhesion molecule 1 (ICAM-1) antibody can significantly inhibit in vitro LAK-induced lysis of cancer cells. A study has shown that ICAM1 in lung cancer cells increases LAK cell-mediated tumor cell death as a new anti-tumor mechanism.[6] One study uses a 4 hour chromium release assay, which is an assay used to measure the cytotoxicity of T cells and natural killer cells, to measure lysis of the fresh solid tumor cells from 10 cancer patients and found that in all 10 cancer patients the fresh autologous tumor cells were resistant to lysis by PBL with natural killer cells, but were lysed by the LAK cells.[7]

Treatment Possible Side Effects

LAK cells, along with the administration of IL-2 have been experimentally used to treat cancer in mice and humans, but there is very high toxicity with this treatment - Severe fluid retention was the major side effect of therapy, although all side effects resolved after interleukin-2 administration was stopped. Treatment of IL-2 cells by themselves to treat cancers are more dangerous than treatment with the combination of IL-2 and LAK cells.[8]

Notes and references

  1. ^ Grimm, E. A.; Mazumder, A.; Zhang, H. Z.; Rosenberg, S. A. (1982-06-01). "Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes". The Journal of Experimental Medicine. 155 (6): 1823–1841. doi:10.1084/jem.155.6.1823. ISSN 0022-1007. PMC 2186695. PMID 6176669.
  2. ^ West, E., Scott, K., Jennings, V. et al. Immune activation by combination human lymphokine-activated killer and dendritic cell therapy. Br J Cancer 105, 787–795 (2011). https://doi.org/10.1038/bjc.2011.290
  3. ^ Rosenberg SA. IL-2: the first effective immunotherapy for human cancer. J Immunol. 2014 Jun 15;192(12):5451-8. doi: 10.4049/jimmunol.1490019. PMID: 24907378; PMCID: PMC6293462.
  4. ^ Maeta N, Tamura K, Takemitsu H, Miyabe M (July 2019). "Lymphokine-activated killer cell transplantation after anti-cancer treatment in two aged cats". Open Veterinary Journal. 9 (2): 147–150. doi:10.4314/ovj.v9i2.9. PMC 6626148. PMID 31360654.
  5. ^ Jennings VA, Ilett EJ, Scott KJ, West EJ, Vile R, Pandha H, et al. (March 2014). "Lymphokine-activated killer and dendritic cell carriage enhances oncolytic reovirus therapy for ovarian cancer by overcoming antibody neutralization in ascites". International Journal of Cancer. 134 (5): 1091–1101. doi:10.1002/ijc.28450. PMC 4321045. PMID 23982804.
  6. ^ Haustein M, Ramer R, Linnebacher M, Manda K, Hinz B (November 2014). "Cannabinoids increase lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1". Biochemical Pharmacology. 92 (2): 312–325. doi:10.1016/j.bcp.2014.07.014. PMID 25069049.
  7. ^ West, E., Scott, K., Jennings, V. et al. Immune activation by combination human lymphokine-activated killer and dendritic cell therapy. Br J Cancer 105, 787–795 (2011). https://doi.org/10.1038/bjc.2011.290
  8. ^ Rosenberg SA, Lotze MT, Yang JC, Aebersold PM, Linehan WM, Seipp CA, White DE. Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients. Ann Surg. 1989 Oct;210(4):474-84; discussion 484-5. doi: 10.1097/00000658-198910000-00008. PMID: 2679456; PMCID: PMC1357927.
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Lymphokine-activated killer cell
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