期刊首页 优先出版 当期阅读 过刊浏览 作者中心 关于期刊 English

《工程(英文)》 >> 2019年 第5卷 第1期 doi: 10.1016/j.eng.2018.11.015

基于自然杀伤细胞的癌症免疫疗法的进展和前景

a Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
b Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei 230061, China

收稿日期: 2018-06-04 修回日期: 2018-10-10 录用日期: 2018-11-29 发布日期: 2018-10-30

下一篇 上一篇

摘要

自然杀伤(natural killer,NK)细胞是重要的先天免疫细胞,位于机体抵御病毒感染和癌症的第一道防线。尽管自然杀伤细胞可以区分“自身”和“非自身”,识别异常细胞,并实时清除恶性转化的细胞和肿瘤,但肿瘤也形成了一些逃逸自然杀伤细胞攻击的策略。这些策略包括:上调自然杀伤细胞抑制性受体的配体,产生可溶性分子或免疫抑制因子。目前,临床试验正在应用各种类型的自然杀伤细胞治疗不同类型的肿瘤,包括自体或同种异体自然杀伤细胞、脐带血(umbilical cord blood,UCB)或诱导性多能干细胞(induced pluripotent stem cell,iPSC)来源的自然杀伤细胞、记忆样自然杀伤细胞和自然杀伤细胞系NK-92 细胞。近来,嵌合抗原受体(chimeric antigen receptor,CAR)修饰的自然杀伤细胞因其再导向特异性和有效的抗肿瘤活性而展现出巨大潜力。文中总结了肿瘤逃逸自然杀伤细胞识别的机制、自然杀伤细胞免疫疗法的现状和进展、提升自然杀伤细胞体内抗肿瘤能力的途径以及该领域在临床实践中所面临的重大挑战。

图片

图1

参考文献

[ 1 ] Cheng M, Chen Y, Xiao W, Sun R, Tian Z. NK cell-based immunotherapy for malignant diseases. Cell Mol Immunol 2013;10(3):230–52. 链接1

[ 2 ] Xiao TS. Innate immunity and inflammation. Cell Mol Immunol 2017;14 (1):1–3. 链接1

[ 3 ] Long EO, Kim HS, Liu D, Peterson ME, Rajagopalan S. Controlling natural killer cell responses: integration of signals for activation and inhibition. Annu Rev Immunol 2013;31(1):227–58. 链接1

[ 4 ] Martinet L, Smyth MJ. Balancing natural killer cell activation through paired receptors. Nat Rev Immunol 2015;15(4):243–54. 链接1

[ 5 ] De Pelsmaeker S, Romero N, Vitale M, Favoreel HW. Herpesvirus evasion of natural killer cells. J Virol 2018;92(11):e02105–17. 链接1

[ 6 ] Sun C, Sun HY, Xiao WH, Zhang C, Tian ZG. Natural killer cell dysfunction in hepatocellular carcinoma and NK cell-based immunotherapy. Acta Pharmacol Sin 2015;36(10):1191–9. 链接1

[ 7 ] Berry R, Ng N, Saunders PM, Vivian JP, Lin J, Deuss FA, et al. Targeting of a natural killer cell receptor family by a viral immunoevasin. Nat Immunol 2013;14(7):699–705. 链接1

[ 8 ] Peng H, Jiang X, Chen Y, Sojka DK, Wei H, Gao X, et al. Liver-resident NK cells confer adaptive immunity in skin-contact inflammation. J Clin Invest 2013;123(4):1444–56. 链接1

[ 9 ] Li T, Wang J, Wang Y, Chen Y, Wei H, Sun R, et al. Respiratory influenza virus infection induces memory-like liver NK cells in mice. J Immunol 2017;198 (3):1242–52. 链接1

[10] Peng H, Sun R. Liver-resident NK cells and their potential functions. Cell Mol Immunol 2017;14:890–4. 链接1

[11] Peng H, Wisse E, Tian Z. Liver natural killer cells: subsets and roles in liver immunity. Cell Mol Immunol 2016;13(3):328–36. 链接1

[12] Marquardt N, Béziat V, Nyström S, Hengst J, Ivarsson MA, Kekäläinen E, et al. Cutting edge: identification and characterization of human intrahepatic CD49a+ NK cells. J Immunol 2015;194(6):2467–71. 链接1

[13] Hydes T, Noll A, Salinas-Riester G, Abuhilal M, Armstrong T, Hamady Z, et al. IL-12 and IL-15 induce the expression of CXCR6 and CD49a on peripheral natural killer cells. Immun Inflamm Dis 2018;6(1):34–46. 链接1

[14] Min-Oo G, Lanier LL. Cytomegalovirus generates long-lived antigen-specific NK cells with diminished bystander activation to heterologous infection. J Exp Med 2014;211(13):2669–80. 链接1

[15] Foley B, Cooley S, Verneris MR, Pitt M, Curtsinger J, Luo X, et al. Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function. Blood 2012;119(11):2665–74. 链接1

[16] Liu LL, Pfefferle A, Yi Sheng VO, Björklund AT, Béziat V, Goodridge JP, et al. Harnessing adaptive natural killer cells in cancer immunotherapy. Mol Oncol 2015;9(10):1904–17. 链接1

[17] Romee R, Schneider SE, Leong JW, Chase JM, Keppel CR, Sullivan RP, et al. Cytokine activation induces human memory-like NK cells. Blood 2012;120 (24):4751–60. 链接1

[18] Romee R, Rosario M, Berrien-Elliott MM, Wagner JA, Jewell BA, Schappe T, et al. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Sci Transl Med 2016;8(357):357ra123. 链接1

[19] Fang F, Xiao W, Tian Z. NK cell-based immunotherapy for cancer. Semin Immunol 2017;31:37–54. 链接1

[20] Daher M, Rezvani K. Next generation natural killer cells for cancer immunotherapy: the promise of genetic engineering. Curr Opin Immunol 2018;51:146–53. 链接1

[21] Maude SL, Teachey DT, Porter DL, Grupp SA. CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood 2015;125 (26):4017–23. 链接1

[22] Rubnitz JE, Inaba H, Ribeiro RC, Pounds S, Rooney B, Bell T, et al. NKAML: a pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia. J Clin Oncol 2010;28(6):955–9. 链接1

[23] Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 2005;105(8):3051–7. 链接1

[24] Shaffer BC, Le Luduec JB, Forlenza C, Jakubowski AA, Perales MA, Young JW, et al. Phase II study of haploidentical natural killer cell infusion for treatment of relapsed or persistent myeloid malignancies following allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2016;22 (4):705–9. 链接1

[25] Han KP, Zhu X, Liu B, Jeng E, Kong L, Yovandich JL, et al. IL-15:IL-15 receptor alpha superagonist complex: high-level co-expression in recombinant mammalian cells, purification and characterization. Cytokine 2011;56 (3):804–10. 链接1

[26] Xu W, Jones M, Liu B, Zhu X, Johnson CB, Edwards AC, et al. Efficacy and mechanism-of-action of a novel superagonist interleukin-15: interleukin-15 receptor aSu/Fc fusion complex in syngeneic murine models of multiple myeloma. Cancer Res 2013;73(10):3075–86. 链接1

[27] Romee R, Cooley S, Berrien-Elliott MM, Westervelt P, Verneris MR, Wagner JE, et al. First-in-human phase 1 clinical study of the IL-15 superagonist complex ALT-803 to treat relapse after transplantation. Blood 2018;131(23):2515–27. 链接1

[28] Rosario M, Liu B, Kong L, Collins LI, Schneider SE, Chen X, et al. The IL-15- based ALT-803 complex enhances FccRIIIa-triggered NK cell responses and in vivo clearance of B cell lymphomas. Clin Cancer Res 2016;22(3):596–608. 链接1

[29] Wagner JA, Rosario M, Romee R, Berrien-Elliott MM, Schneider SE, Leong JW, et al. CD56bright NK cells exhibit potent antitumor responses following IL-15 priming. J Clin Invest 2017;127(11):4042–58. 链接1

[30] Felices M, Chu S, Kodal B, Bendzick L, Ryan C, Lenvik AJ, et al. IL-15 superagonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer. Gynecol Oncol 2017;145(3):453–61. 链接1

[31] Veuillen C, Aurran-Schleinitz T, Castellano R, Rey J, Mallet F, Orlanducci F, et al. Primary B-CLL resistance to NK cell cytotoxicity can be overcome in vitro and in vivo by priming NK cells and monoclonal antibody therapy. J Clin Immunol 2012;32(3):632–46. 链接1

[32] Reiners KS, Kessler J, Sauer M, Rothe A, Hansen HP, Reusch U, et al. Rescue of impaired NK cell activity in Hodgkin lymphoma with bispecific antibodies in vitro and in patients. Mol Ther 2013;21(4):895–903. 链接1

[33] Paul S, Kulkarni N, Shilpi Lal G. Intratumoral natural killer cells show reduced effector and cytolytic properties and control the differentiation of effector Th1 cells. OncoImmunology 2016;5(12):e1235106. 链接1

[34] Ibrahim EC, Guerra N, Lacombe MJ, Angevin E, Chouaib S, Carosella ED, et al. Tumor-specific up-regulation of the nonclassical class I HLA-G antigen expression in renal carcinoma. Cancer Res 2001;61(18):6838–45. 链接1

[35] Polakova K, Bandzuchova E, Sabty FA, Mistrik M, Demitrovicova L, Russ G. Activation of HLA-G expression by 5-aza’-2-deoxycytidine in malignant hematopoietic cells isolated from leukemia patients. Neoplasma 2009;56 (6):514–20. 链接1

[36] Wan R, Wang ZW, Li H, Peng XD, Liu GY, Ou JM, et al. Human leukocyte antigen-G inhibits the anti-tumor effect of natural killer cells via immunoglobulin-like transcript 2 in gastric cancer. Cell Physiol Biochem 2017;44(5):1828–41. 链接1

[37] Kailayangiri S, Altvater B, Spurny C, Jamitzky S, Schelhaas S, Jacobs AH, et al. Targeting Ewing sarcoma with activated and GD2-specific chimeric antigen receptor-engineered human NK cells induces upregulation of immuneinhibitory HLA-G. OncoImmunology 2017;6(1):e1250050. 链接1

[38] Maki G, Hayes GM, Naji A, Tyler T, Carosella ED, Rouas-Freiss N, et al. NK resistance of tumor cells from multiple myeloma and chronic lymphocytic leukemia patients: implication of HLA-G. Leukemia 2008;22(5):998–1006. 链接1

[39] Chiu J, Ernst DM, Keating A. Acquired natural killer cell dysfunction in the tumor microenvironment of classic Hodgkin lymphoma. Front Immunol 2018;9:267. 链接1

[40] Reiners KS, Topolar D, Henke A, Simhadri VR, Kessler J, Sauer M, et al. Soluble ligands for NK cell receptors promote evasion of chronic lymphocytic leukemia cells from NK cell anti-tumor activity. Blood 2013;121 (18):3658–65. 链接1

[41] Binici J, Hartmann J, Herrmann J, Schreiber C, Beyer S, Güler G, et al. A soluble fragment of the tumor antigen BCL2-associated athanogene 6 (BAG-6) is essential and sufficient for inhibition of NKp30 receptor-dependent cytotoxicity of natural killer cells. J Biol Chem 2013;288(48):34295–303. 链接1

[42] Fernández-Messina L, Ashiru O, Boutet P, Agüera-González S, Skepper JN, Reyburn HT, et al. Differential mechanisms of shedding of the glycosylphosphatidylinositol (GPI)-anchored NKG2D ligands. J Biol Chem 2010;285(12):8543–51. 链接1

[43] Pogge von Strandmann E, Simhadri VR, von Tresckow B, Sasse S, Reiners KS, Hansen HP, et al. Human leukocyte antigen-B-associated transcript 3 is released from tumor cells and engages the NKp30 receptor on natural killer cells. Immunity 2007;27(6):965–74. 链接1

[44] Zocchi MR, Catellani S, Canevali P, Tavella S, Garuti A, Villaggio B, et al. High ERp5/ADAM10 expression in lymph node microenvironment and impaired NKG2D ligands recognition in Hodgkin lymphomas. Blood 2012;119 (6):1479–89. 链接1

[45] Ferrari de Andrade L, Tay RE, Pan D, Luoma AM, Ito Y, Badrinath S, et al. Antibody-mediated inhibition of MICA and MICB shedding promotes NK celldriven tumor immunity. Science 2018;359(6383):1537–42. 链接1

[46] Joyce JA, Fearon DT. T cell exclusion, immune privilege, and the tumor microenvironment. Science 2015;348(6230):74–80. 链接1

[47] Tang H, Qiao J, Fu YX. Immunotherapy and tumor microenvironment. Cancer Lett 2016;370(1):85–90. 链接1

[48] Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merad M, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med 2018;24(5):541–50. 链接1

[49] Mion F, Tonon S, Valeri V, Pucillo CE. Message in a bottle from the tumor microenvironment: tumor-educated DCs instruct B cells to participate in immunosuppression. Cell Mol Immunol 2017;14(9):730–2. 链接1

[50] Baginska J, Viry E, Paggetti J, Medves S, Berchem G, Moussay E, et al. The critical role of the tumor microenvironment in shaping natural killer cellmediated anti-tumor immunity. Front Immunol 2013;4:490. 链接1

[51] Pietra G, Manzini C, Rivara S, Vitale M, Cantoni C, Petretto A, et al. Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity. Cancer Res 2012;72(6):1407–15. 链接1

[52] Balsamo M, Scordamaglia F, Pietra G, Manzini C, Cantoni C, Boitano M, et al. Melanoma-associated fibroblasts modulate NK cell phenotype and antitumor cytotoxicity. Proc Natl Acad Sci USA 2009;106(49):20847–52. 链接1

[53] Li H, Han Y, Guo Q, Zhang M, Cao X. Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-b1. J Immunol 2009;182(1):240–9. 链接1

[54] Cekic C, Day YJ, Sag D, Linden J. Myeloid expression of adenosine A2A receptor suppresses T and NK cell responses in the solid tumor microenvironment. Cancer Res 2014;74(24):7250–9. 链接1

[55] Bi J, Tian Z. NK cell exhaustion. Front Immunol 2017;8:760. 链接1

[56] Sun C, Xu J, Huang Q, Huang M, Wen H, Zhang C, et al. High NKG2A expression contributes to NK cell exhaustion and predicts a poor prognosis of patients with liver cancer. OncoImmunology 2017;6(1):e1264562. 链接1

[57] Zhang QF, Yin WW, Xia Y, Yi YY, He QF, Wang X, et al. Liver-infiltrating CD11bCD27 NK subsets account for NK-cell dysfunction in patients with hepatocellular carcinoma and are associated with tumor progression. Cell Mol Immunol 2017;14(10):819–29. 链接1

[58] Krneta T, Gillgrass A, Chew M, Ashkar AA. The breast tumor microenvironment alters the phenotype and function of natural killer cells. Cell Mol Immunol 2016;13(5):628–39. 链接1

[59] Zhang Q, Bi J, Zheng X, Chen Y, Wang H, Wu W, et al. Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent antitumor immunity. Nat Immunol 2018;19(7):723–32. 链接1

[60] Rosenberg SA. Immunotherapy of cancer by systemic administration of lymphoid cells plus interleukin-2. J Biol Response Mod 1984;3(5):501–11. 链接1

[61] Sakamoto N, Ishikawa T, Kokura S, Okayama T, Oka K, Ideno M, et al. Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer. J Transl Med 2015;13(1):277. 链接1

[62] Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002;295(5562):2097–100. 链接1

[63] Bachanova V, Burns LJ, McKenna DH, Curtsinger J, Panoskaltsis-Mortari A, Lindgren BR, et al. Allogeneic natural killer cells for refractory lymphoma. Cancer Immunol Immunother 2010;59(11):1739–44. 链接1

[64] Bachanova V, Sarhan D, DeFor TE, Cooley S, Panoskaltsis-Mortari A, Blazar BR, et al. Haploidentical natural killer cells induce remissions in non-Hodgkin lymphoma patients with low levels of immune-suppressor cells. Cancer Immunol Immunother 2018;67(3):483–94. 链接1

[65] Björklund AT, Carlsten M, Sohlberg E, Liu LL, Clancy T, Karimi M, et al. Complete remission with reduction of high-risk clones following haploidentical NK-cell therapy against MDS and AML. Clin Cancer Res 2018;24(8):1834–44. 链接1

[66] Curti A, Ruggeri L, D’Addio A, Bontadini A, Dan E, Motta MR, et al. Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. Blood 2011;118(12):3273–9. 链接1

[67] Geller MA, Cooley S, Judson PL, Ghebre R, Carson LF, Argenta PA, et al. A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer. Cytotherapy 2011;13(1):98–107. 链接1

[68] Ishikawa T, Okayama T, Sakamoto N, Ideno M, Oka K, Enoki T, et al. Phase I clinical trial of adoptive transfer of expanded natural killer cells in combination with IgG1 antibody in patients with gastric or colorectal cancer. Int J Cancer 2018;142(12):2599–609. 链接1

[69] Lee DA, Denman CJ, Rondon G, Woodworth G, Chen J, Fisher T, et al. Haploidentical natural killer cells infused before allogeneic stem cell transplantation for myeloid malignancies: a phase I trial. Biol Blood Marrow Transplant 2016;22(7):1290–8. 链接1

[70] Adotevi O, Godet Y, Galaine J, Lakkis Z, Idirene I, Certoux JM, et al. In situ delivery of allogeneic natural killer cell (NK) combined with Cetuximab in liver metastases of gastrointestinal carcinoma: a phase I clinical trial. OncoImmunology 2018;7(5):e1424673. 链接1

[71] Ciurea SO, Schafer JR, Bassett R, Denman CJ, Cao K, Willis D, et al. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation. Blood 2017;130(16):1857–68. 链接1

[72] Bachanova V, Cooley S, Defor TE, Verneris MR, Zhang B, McKenna DH, et al. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood 2014;123 (25):3855–63. 链接1

[73] Pillet AH, Thèze J, Rose T. Interleukin (IL)-2 and IL-15 have different effects on human natural killer lymphocytes. Hum Immunol 2011;72(11):1013–7. 链接1

[74] Chen Y, Chen B, Yang T, Xiao W, Qian L, Ding Y, et al. Human fused NKG2D-IL- 15 protein controls xenografted human gastric cancer through the recruitment and activation of NK cells. Cell Mol Immunol 2017;14 (3):293–307. 链接1

[75] Spanholtz J, Tordoir M, Eissens D, Preijers F, van der Meer A, Joosten I, et al. High log-scale expansion of functional human natural killer cells from umbilical cord blood CD34-positive cells for adoptive cancer immunotherapy. PLoS ONE 2010;5(2):e9221. 链接1

[76] Knorr DA, Ni Z, Hermanson D, Hexum MK, Bendzick L, Cooper LJ, et al. Clinical-scale derivation of natural killer cells from human pluripotent stem cells for cancer therapy. Stem Cells Transl Med 2013;2(4):274–83. 链接1

[77] Herrera L, Salcedo JM, Santos S, Vesga MA, Borrego F, Eguizabal C. OP9 feeder cells are superior to M2–10B4 cells for the generation of mature and functional natural killer cells from umbilical cord hematopoietic progenitors. Front Immunol 2017;8:755. 链接1

[78] Hermanson DL, Bendzick L, Pribyl L, McCullar V, Vogel RI, Miller JS, et al. Induced pluripotent stem cell-derived natural killer cells for treatment of ovarian cancer. Stem Cells 2016;34(1):93–101. 链接1

[79] Zeng J, Tang SY, Toh LL, Wang S. Generation of ‘‘off-the-shelf” natural killer cells from peripheral blood cell-derived induced pluripotent stem cells. Stem Cell Rep 2017;9(6):1796–812. 链接1

[80] Xing D, Ramsay AG, Gribben JG, Decker WK, Burks JK, Munsell M, et al. Cord blood natural killer cells exhibit impaired lytic immunological synapse formation that is reversed with IL-2 ex vivo expansion. J Immunother 2010;33 (7):684–96. 链接1

[81] Veluchamy JP, Lopez-Lastra S, Spanholtz J, Bohme F, Kok N, Heideman DA, et al. In vivo efficacy of umbilical cord blood stem cell-derived NK cells in the treatment of metastatic colorectal cancer. Front Immunol 2017;8:87. 链接1

[82] Ichise H, Nagano S, Maeda T, Miyazaki M, Miyazaki Y, Kojima H, et al. NK cell alloreactivity against KIR-ligand-mismatched HLA-haploidentical tissue derived from HLA haplotype-homozygous iPSCs. Stem Cell Rep 2017;9 (3):853–67. 链接1

[83] Lehmann D, Spanholtz J, Sturtzel C, Tordoir M, Schlechta B, Groenewegen D, et al. IL-12 directs further maturation of ex vivo differentiated NK cells with improved therapeutic potential. PLoS ONE 2014;9(1):e87131. 链接1

[84] Veluchamy JP, Heeren AM, Spanholtz J, van Eendenburg JD, Heideman DA, Kenter GG, et al. High-efficiency lysis of cervical cancer by allogeneic NK cells derived from umbilical cord progenitors is independent of HLA status. Cancer Immunol Immunother 2017;66(1):51–61. 链接1

[85] Boudreau JE, Hsu KC. Natural killer cell education in human health and disease. Curr Opin Immunol 2018;50:102–11. 链接1

[86] Boudreau JE, Hsu KC. Natural killer cell education and the response to infection and cancer therapy: stay tuned. Trends Immunol 2018;39 (3):222–39. 链接1

[87] Sarvaria A, Jawdat D, Madrigal JA, Saudemont A. Umbilical cord blood natural killer cells, their characteristics, and potential clinical applications. Front Immunol 2017;8:329. 链接1

[88] He Y, Tian Z. NK cell education via nonclassical MHC and non-MHC ligands. Cell Mol Immunol 2017;14(4):321–30. 链接1

[89] Tam YK, Miyagawa B, Ho VC, Klingemann HG. Immunotherapy of malignant melanoma in a SCID mouse model using the highly cytotoxic natural killer cell line NK-92. J Hematother 1999;8(3):281–90. 链接1

[90] Cheng M, Zhang J, Jiang W, Chen Y, Tian Z. Natural killer cell lines in tumor immunotherapy. Front Med 2012;6(1):56–66. 链接1

[91] Cheng M, Ma J, Chen Y, Zhang J, Zhao W, Zhang J, et al. Establishment, characterization, and successful adaptive therapy against human tumors of NKG cell, a new human NK cell line. Cell Transplant 2011;20(11– 12):1731–46. 链接1

[92] Tonn T, Becker S, Esser R, Schwabe D, Seifried E. Cellular immunotherapy of malignancies using the clonal natural killer cell line NK-92. J Hematother Stem Cell Res 2001;10(4):535–44. 链接1

[93] Arai S, Meagher R, Swearingen M, Myint H, Rich E, Martinson J, et al. Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial. Cytotherapy 2008;10(6):625–32. 链接1

[94] Tonn T, Schwabe D, Klingemann HG, Becker S, Esser R, Koehl U, et al. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy 2013;15(12):1563–70. 链接1

[95] Boyiadzis M, Agha M, Redner RL, Sehgal A, Im A, Hou JZ, et al. Phase 1 clinical trial of adoptive immunotherapy using ‘‘off-the-shelf” activated natural killer cells in patients with refractory and relapsed acute myeloid leukemia. Cytotherapy 2017;19(10):1225–32. 链接1

[96] Gong JH, Maki G, Klingemann HG. Characterization of a human cell line (NK- 92) with phenotypical and functional characteristics of activated natural killer cells. Leukemia 1994;8(4):652–8. 链接1

[97] Paul S, Lal G. The molecular mechanism of natural killer cells function and its importance in cancer immunotherapy. Front Immunol 2017;8:1124. 链接1

[98] Ni J, Miller M, Stojanovic A, Garbi N, Cerwenka A. Sustained effector function of IL-12/15/18-preactivated NK cells against established tumors. J Exp Med 2012;209(13):2351–65. 链接1

[99] Leong JW, Chase JM, Romee R, Schneider SE, Sullivan RP, Cooper MA, et al. Preactivation with IL-12, IL-15, and IL-18 induces CD25 and a functional highaffinity IL-2 receptor on human cytokine-induced memory-like natural killer cells. Biol Blood Marrow Transplant 2014;20(4):463–73. 链接1

[100] Newhook N, Fudge N, Grant M. NK cells generate memory-type responses to human cytomegalovirus-infected fibroblasts. Eur J Immunol 2017;47 (6):1032–9. 链接1

[101] Bigley AB, Rezvani K, Shah N, Sekine T, Balneger N, Pistillo M, et al. Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans. Clin Exp Immunol 2016;185(2):239–51. 链接1

[102] Liu LL, Béziat V, Oei VYS, Pfefferle A, Schaffer M, Lehmann S, et al. Ex vivo expanded adaptive NK cells effectively kill primary acute lymphoblastic leukemia cells. Cancer Immunol Res 2017;5(8):654–65. 链接1

[103] Peng H, Tian Z. Natural killer cell memory: progress and implications. Front Immunol 2017;8:1143. 链接1

[104] Oei VYS, Siernicka M, Graczyk-Jarzynka A, Hoel HJ, Yang W, Palacios D, et al. Intrinsic functional potential of NK-cell subsets constrains retargeting driven by chimeric antigen receptors. Cancer Immunol Res 2018;6(4):467–80. 链接1

[105] Peng H, Tian Z. Tissue-resident natural killer cells in the livers. Sci China Life Sci 2016;59(12):1218–23. 链接1

[106] Robinson MW, Harmon C, O’Farrelly C. Liver immunology and its role in inflammation and homeostasis. Cell Mol Immunol 2016;13(3):267–76. 链接1

[107] Jackson HJ, Rafiq S, Brentjens RJ. Driving CAR T-cells forward. Nat Rev Clin Oncol 2016;13(6):370–83. 链接1

[108] Johnson LA, June CH. Driving gene-engineered T cell immunotherapy of cancer. Cell Res 2017;27(1):38–58. 链接1

[109] Bedoya F, Frigault MJ, Maus MV. The flipside of the power of engineered T cells: observed and potential toxicities of genetically modified T cells as therapy. Mol Ther 2017;25(2):314–20. 链接1

[110] Hu Y, Tian ZG, Zhang C. Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy. Acta Pharmacol Sin 2018;39(2):167–76. 链接1

[111] Han J, Chu J, Keung Chan W, Zhang J, Wang Y, Cohen JB, et al. CAR-engineered NK cells targeting wild-type EGFR and EGFRvIII enhance killing of glioblastoma and patient-derived glioblastoma stem cells. Sci Rep 2015;5 (1):11483. 链接1

[112] Yu M, Luo H, Fan M, Wu X, Shi B, Di S, et al. Development of GPC3-specific chimeric antigen receptor-engineered natural killer cells for the treatment of hepatocellular carcinoma. Mol Ther 2018;26(2):366–78. 链接1

[113] Shimasaki N, Fujisaki H, Cho D, Masselli M, Lockey T, Eldridge P, et al. A clinically adaptable method to enhance the cytotoxicity of natural killer cells against B-cell malignancies. Cytotherapy 2012;14(7):830–40. 链接1

[114] Oelsner S, Friede ME, Zhang C, Wagner J, Badura S, Bader P, et al. Continuously expanding CAR NK-92 cells display selective cytotoxicity against B-cell leukemia and lymphoma. Cytotherapy 2017;19(2):235–49. 链接1

[115] Müller T, Uherek C, Maki G, Chow KU, Schimpf A, Klingemann HG, et al. Expression of a CD20-specific chimeric antigen receptor enhances cytotoxic activity of NK cells and overcomes NK-resistance of lymphoma and leukemia cells. Cancer Immunol Immunother 2008;57(3):411–23. 链接1

[116] Schirrmann T, Pecher G. Specific targeting of CD33+ leukemia cells by a natural killer cell line modified with a chimeric receptor. Leuk Res 2005;29 (3):301–6. 链接1

[117] Jiang H, Zhang W, Shang P, Zhang H, Fu W, Ye F, et al. Transfection of chimeric anti-CD138 gene enhances natural killer cell activation and killing of multiple myeloma cells. Mol Oncol 2014;8(2):297–310. 链接1

[118] Chu J, Deng Y, Benson DM, He S, Hughes T, Zhang J, et al. CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma. Leukemia 2014;28(4):917–27. 链接1

[119] Uherek C, Tonn T, Uherek B, Becker S, Schnierle B, Klingemann HG, et al. Retargeting of natural killer-cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction. Blood 2002;100 (4):1265–73. 链接1

[120] Töpfer K, Cartellieri M, Michen S, Wiedemuth R, Müller N, Lindemann D, et al. DAP12-based activating chimeric antigen receptor for NK cell tumor immunotherapy. J Immunol 2015;194(7):3201–12. 链接1

[121] Zhang C, Burger MC, Jennewein L, Genßler S, Schönfeld K, Zeiner P, et al. ErbB2/HER2-specific NK cells for targeted therapy of glioblastoma. J Natl Cancer Inst 2015;108(5):djv375. 链接1

[122] Zhang G, Liu R, Zhu X, Wang L, Ma J, Han H, et al. Retargeting NK-92 for antimelanoma activity by a TCR-like single-domain antibody. Immunol Cell Biol 2013;91(10):615–24. 链接1

[123] Müller N, Michen S, Tietze S, Töpfer K, Schulte A, Lamszus K, et al. Engineering NK cells modified with an EGFRvIII-specific chimeric antigen receptor to overexpress CXCR4 Improves Immunotherapy of CXCL12/SDF- 1a-secreting glioblastoma. J Immunother 2015;38(5):197–210. 链接1

[124] Liu E, Tong Y, Dotti G, Shaim H, Savoldo B, Mukherjee M, et al. Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show longterm persistence and potent antitumor activity. Leukemia 2018;32 (2):520–31. 链接1

[125] Altvater B, Landmeier S, Pscherer S, Temme J, Schweer K, Kailayangiri S, et al. 2B4 (CD244) signaling by recombinant antigen-specific chimeric receptors costimulates natural killer cell activation to leukemia and neuroblastoma cells. Clin Cancer Res 2009;15(15):4857–66. 链接1

[126] Li Y, Hermanson DL, Moriarity BS, Kaufman DS. Human iPSC-derived natural killer cells engineered with chimeric antigen receptors enhance anti-tumor activity. Cell Stem Cell 2018;23(2):181–92. 链接1

[127] Hsu J, Hodgins JJ, Marathe M, Nicolai CJ, Bourgeois-Daigneault MC, Trevino TN, et al. Contribution of NK cells to immunotherapy mediated by PD-1/PDL1 blockade. J Clin Invest 2018;128(10):4654–68. 链接1

[128] Pesce S, Greppi M, Tabellini G, Rampinelli F, Parolini S, Olive D, et al. Identification of a subset of human natural killer cells expressing high levels of programmed death 1: a phenotypic and functional characterization. J Allergy Clin Immunol 2017;139(1):335–46. 链接1

[129] Dougall WC, Kurtulus S, Smyth MJ, Anderson AC. TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy. Immunol Rev 2017;276(1):112–20. 链接1

[130] Chew GM, Fujita T, Webb GM, Burwitz BJ, Wu HL, Reed JS, et al. TIGIT marks exhausted t cells, correlates with disease progression, and serves as a target for immune restoration in HIV and SIV infection. PLoS Pathog 2016;12(1): e1005349. 链接1

[131] Chauvin JM, Pagliano O, Fourcade J, Sun Z, Wang H, Sander C, et al. TIGIT and PD-1 impair tumor antigen-specific CD8+ T cells in melanoma patients. J Clin Invest 2015;125(5):2046–58. 链接1

[132] Da Silva IP, Gallois A, Jimenez-Baranda S, Khan S, Anderson AC, Kuchroo VK, et al. Reversal of NK-cell exhaustion in advanced melanoma by Tim-3 blockade. Cancer Immunol Res 2014;2(5):410–22. 链接1

[133] Guillerey C, Huntington ND, Smyth MJ. Targeting natural killer cells in cancer immunotherapy. Nat Immunol 2016;17(9):1025–36. 链接1

相关研究