In cell biology, a lymphokine-activated killer cell (also known as a LAK cell) is a white blood cell that has been stimulated to kill tumor cells.[1] If lymphocytes are cultured in the presence of Interleukin 2, it results in the development of effector cells which are cytotoxic to tumor cells.[2]

Mechanism

It has been shown that lymphocytes, when exposed to Interleukin 2, are capable of lysing fresh, non-cultured cancer cells, both primary and metastatic.[3] LAK cells respond to these lymphokines, particularly IL-2, by lysing tumor cells that were already known to be resistant to NK cell activity.[4]

The mechanism of LAK cells is distinctive from that of natural killer cells because they can lyse cells that NK cells cannot.[4] 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.[4] LAK cells are specific to tumor cells and do not display activity against normal cells.[4]

Cancer Treatment

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.[5] 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.[6] 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.[7] 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.[8]

Notes and references

  1. ^ "Definition of lymphokine-activated killer cell". National Cancer Institute. Retrieved 2007-03-06.
  2. ^ "Medical Dictionary: Lymphokine-activated killer cell". Wrong Diagnosis. Retrieved 2007-03-06.
  3. ^ Fagan EA, Eddleston AL (February 1987). "Immunotherapy for cancer: the use of lymphokine activated killer (LAK) cells". Gut. 28 (2): 113–116. doi:10.1136/gut.28.2.113. PMC 1432985. PMID 3549471.
  4. ^ a b c d Lafreniere R, Rosenberg SA (1985). "Successful immunotherapy of murine experimental hepatic metastases with lymphokine-activated killer cells and recombinant Interleukin 2". Cancer Res. 45: 3735–41. PMID 3893689.
  5. ^ Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, et al. (December 1985). "Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer". The New England Journal of Medicine. 313 (23): 1485–1492. doi:10.1056/nejm198512053132327. PMID 3903508.
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.

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