Biology:Lymphokine-activated killer cell

From HandWiki

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. http://www.cancer.gov/dictionary?CdrID=45287. 
  2. "Medical Dictionary: Lymphokine-activated killer cell". Wrong Diagnosis. http://www.wrongdiagnosis.com/medical/lymphokine_activated_killer_cell.htm. 
  3. "Immunotherapy for cancer: the use of lymphokine activated killer (LAK) cells". Gut 28 (2): 113–116. February 1987. doi:10.1136/gut.28.2.113. PMID 3549471. 
  4. 4.0 4.1 4.2 4.3 "Successful immunotherapy of murine experimental hepatic metastases with lymphokine-activated killer cells and recombinant Interleukin 2.". Cancer Res 45: 3735–41. 1985. PMID 3893689. 
  5. "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. December 1985. doi:10.1056/nejm198512053132327. PMID 3903508. 
  6. "Lymphokine-activated killer cell transplantation after anti-cancer treatment in two aged cats". Open Veterinary Journal 9 (2): 147–150. July 2019. doi:10.4314/ovj.v9i2.9. PMID 31360654. 
  7. "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. March 2014. doi:10.1002/ijc.28450. PMID 23982804. 
  8. "Cannabinoids increase lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1". Biochemical Pharmacology 92 (2): 312–325. November 2014. doi:10.1016/j.bcp.2014.07.014. PMID 25069049. 

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