NK cells in therapy of cancer.
NK cells in therapy of cancer.
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DOI：
10.1615/critrevoncog.2014011091
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发表时间：
2014
影响因子：
--
通讯作者：
Miller JS
中科院分区：
文献类型：
--
作者：
Bachanova V;Miller JS
自然杀伤细胞（NK）可以识别恶性转化或感染的目标，并且可以长期存活。它们通过与主要组织相容性抗原（MHC） I类分子相互作用而获得杀死靶标和产生细胞因子的功能。在临床上，单倍体NK细胞可以过继性转移治疗癌症。NK细胞的持续存在和体内扩张依赖于淋巴消耗化疗来制造空间并诱导内源性IL-15的释放。在体内，细胞因子的使用也能促进细胞的扩张，但IL-2有刺激CD25hi调节性T细胞（Tregs）的不利作用。nk细胞治疗的其他限制包括体内存活率差和缺乏特异性。双特异性或三特异性杀伤接合体靶向NK细胞上的CD16以增强对肿瘤抗原的识别，以及在NK细胞活化后抑制CD16脱落的去整合素和金属蛋白酶17 （ADAM17）抑制作用应能促进特异性地增强对癌症的杀伤。这是激动人心的时刻；在NK细胞最初被描述超过35年后，我们正在利用它们的临床治疗能力。
Natural killer (NK) cells recognize targets stressed by malignant transformation or infection and can be long-lived. They become educated by interacting with major histocompatibility antigen (MHC) class I molecules to gain function to kill targets and produce cytokines. In the clinic, haploidentical NK cells can be adoptively transferred to treat cancer. Persistence and in vivo expansion of NK cells depends on lymphodepleting chemotherapy to make space and induce release of endogenous IL-15. In vivo expansion is also enhanced by cytokine administration but IL-2 has the down side of stimulating CD25hi regulatory T cells (Tregs). Other limitations to NK-cell therapy include poor in vivo survival and lack of specificity. Bispecific or trispecific killer engagers that target CD16 on NK cells to enhance recognition of tumor antigens, and desintegrin and metalloproteinase 17 (ADAM17) inhibition that prevents CD16 shedding after NK-cell activation should promote enhanced killing of cancer with specificity. These are exciting times; more than 35 years after NK cells were initially described, we are exploiting their capacity for clinical therapy.