6.1　Lymphokine-Activated Killer

Lymphokine-activated killer cells (LAKs) are a heterogeneous population of cells consisting primarily of NK, NKT and T cells, which are generated in vitro by culture of peripheral blood mononuclear cells (PBMCs) in IL-2.The predominant effector cells within LAKs are NK cells,which are mechanistically equivalent to peripheral blood NK cells, but are more cytotoxic against tumor cells, including otherwise NK resistant targets.Moreover, LAKs are more readily cultured in large numbers for administration to patients than purified NK cells.LAKs have previously been shown to localize to tumor sites in both mouse and human systems, and therefore have the potential to access and lyse tumors in patients following systemic administration in vivo.Although there was considerable clinical interest in LAKs for cancer therapy towards the end of the last century, their application for patients has not progressed, in part due to concerns about the toxicity associated with IL-2, which had to be co-administered to maintain LAK activation in vivo [1].(https://www.daowen.com)

LAK cells (a heterogeneous population of activated T, NK and NKT cells), which can be easily cultured in large numbers from patients, have shown some promise as a celllular agent for cancer therapy and have been used clinically with IL-2 for the treatment of ovarian cancer.LAK cells show specific antitumor activity against autologous ovarian tumor cells and can be expanded ex vivo in the presence of IL-2.However, whilst LAK cells alone were well tolerated (up to 1011 cells per infusion), concomitant systemic delivery of IL-2 to patients resulted in significant toxicities,including vascular leakage and hypotension [1].