1932

Abstract

Immunotherapy is at the forefront of cancer treatment. The advent of numerous novel approaches to cancer immunotherapy, including immune checkpoint antibodies, adoptive transfer of CAR (chimeric antigen receptor) T cells and TCR (T cell receptor) T cells, NK (natural killer) cells, T cell engagers, oncolytic viruses, and vaccines, is revolutionizing the treatment for different tumor types. Some are already in the clinic, and many others are underway. However, not all patients respond, resistance develops, and as available therapies multiply there is a need to further understand how they work, how to prioritize their clinical evaluation, and how to combine them. For this, animal models have been highly instrumental, and humanized mice models (i.e., immunodeficient mice engrafted with human immune and cancer cells) represent a step forward, although they have several limitations. Here, we review the different humanized models available today, the approaches to overcome their flaws, their use for the evaluation of cancer immunotherapies, and their anticipated evolution as tools to help personalized clinical decision-making.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cancerbio-050520-100526
2021-03-04
2024-06-24
Loading full text...

Full text loading...

/deliver/fulltext/cancerbio/5/1/annurev-cancerbio-050520-100526.html?itemId=/content/journals/10.1146/annurev-cancerbio-050520-100526&mimeType=html&fmt=ahah

Literature Cited

  1. Anderson BE, McNiff J, Yan J, Doyle H, Mamula M et al. 2003. Memory CD4+ T cells do not induce graft-versus-host disease. J. Clin. Investig. 112:101–8
    [Google Scholar]
  2. Bacac M, Fauti T, Sam J, Colombetti S, Weinzierl T et al. 2016a. A novel carcinoembryonic antigen T-cell bispecific antibody (CEA TCB) for the treatment of solid tumors. Clin. Cancer Res. 22:3286–97
    [Google Scholar]
  3. Bacac M, Klein C, Umana P 2016b. CEA TCB: a novel head-to-tail 2:1 T cell bispecific antibody for treatment of CEA-positive solid tumors. OncoImmunology 5:e1203498
    [Google Scholar]
  4. Barry WE, Jackson JR, Asuelime GE, Wu H-W, Sun J et al. 2019. Activated natural killer cells in combination with anti-GD2 antibody dinutuximab improve survival of mice after surgical resection of primary neuroblastoma. Clin. Cancer Res. 25:325–33
    [Google Scholar]
  5. Barve A, Casson L, Krem M, Wunderlich M, Mulloy JC, Beverly LJ 2018. Comparative utility of NRG and NRGS mice for the study of normal hematopoiesis, leukemogenesis, and therapeutic response. Exp. Hematol. 67:18–31
    [Google Scholar]
  6. Billerbeck E, Barry WT, Mu K, Dorner M, Rice CM, Ploss A 2011. Development of human CD4+FoxP3+ regulatory T cells in human stem cell factor-, granulocyte-macrophage colony-stimulating factor-, and interleukin-3-expressing NOD-SCID IL2Rγnull humanized mice. Blood 117:3076–86
    [Google Scholar]
  7. Bosma GC, Custer RP, Bosma MJ 1983. A severe combined immunodeficiency mutation in the mouse. Nature 301:527–30
    [Google Scholar]
  8. Boudreau JE, Liu XR, Zhao Z, Zhang A, Shultz LD et al. 2016. Cell-extrinsic MHC class I molecule engagement augments human NK cell education programmed by cell-intrinsic MHC class I. Immunity 45:280–91
    [Google Scholar]
  9. Brainard DM, Seung E, Frahm N, Cariappa A, Bailey CC et al. 2009. Induction of robust cellular and humoral virus-specific adaptive immune responses in human immunodeficiency virus-infected humanized BLT mice. J. Virol. 83:7305–21
    [Google Scholar]
  10. Brehm MA, Aryee K-E, Bruzenksi L, Greiner DL, Shultz LD, Keck J 2018. Transgenic expression of human IL15 in NOD-scid IL2rgnull (NSG) mice enhances the development and survival of functional human NK cells. J. Immunol. 200:1 Suppl.103.20
    [Google Scholar]
  11. Brehm MA, Bortell R, Verma M, Shultz LD, Greiner DL 2016. Humanized mice in translational immunology. Translational Immunology: Mechanisms and Pharmacologic Approaches S-L Tan 285–326 Amsterdam: Academic
    [Google Scholar]
  12. Brehm MA, Kenney LL, Wiles MV, Low BE, Tisch RM et al. 2019. Lack of acute xenogeneic graft-versus-host disease, but retention of T-cell function following engraftment of human peripheral blood mononuclear cells in NSG mice deficient in MHC class I and II expression. FASEB J 33:33137–51
    [Google Scholar]
  13. Burlion A, Ramos RN, Pukar KC, Sendeyo K, Corneau A et al. 2019. A novel combination of chemotherapy and immunotherapy controls tumor growth in mice with a human immune system. OncoImmunology 8:71596005
    [Google Scholar]
  14. Capasso A, Lang J, Pitts TM, Jordan KR, Lieu CH et al. 2019. Characterization of immune responses to anti-PD-1 mono and combination immunotherapy in hematopoietic humanized mice implanted with tumor xenografts. J. Immunother. Cancer 7:37
    [Google Scholar]
  15. Casucci M, Nicolis di Robilant B, Falcone L, Camisa B, Norelli M et al. 2013. CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma. Blood 122:3461–72
    [Google Scholar]
  16. Chen BJ, Cui X, Sempowski GD, Liu C, Chao NJ 2004. Transfer of allogeneic CD62L memory T cells without graft-versus-host disease. Blood 103:1534–41
    [Google Scholar]
  17. Chen Q, He F, Kwang J, Chan JKY, Chen J 2012. GM-CSF and IL-4 stimulate antibody responses in humanized mice by promoting T, B, and dendritic cell maturation. J. Immunol. 189:5223–29
    [Google Scholar]
  18. Chen Q, Khoury M, Chen J 2009. Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice. PNAS 106:21783–88
    [Google Scholar]
  19. Covassin L, Jangalwe S, Jouvet N, Laning J, Burzenski L et al. 2013. Human immune system development and survival of non-obese diabetic (NOD)-scid IL2rγnull (NSG) mice engrafted with human thymus and autologous haematopoietic stem cells. Clin. Exp. Immunol. 174:372–88
    [Google Scholar]
  20. Covassin L, Laning J, Abdi R, Langevin DL, Phillips NE et al. 2011. Human peripheral blood CD4 T cell-engrafted non-obese diabetic-scid IL2rγnullH2-Ab1tm1Gru Tg (human leucocyte antigen D-related 4) mice: a mouse model of human allogeneic graft-versus-host disease. Clin. Exp. Immunol. 166:269–80
    [Google Scholar]
  21. Danner R, Chaudhari SN, Rosenberger J, Surls J, Richie TL et al. 2011. Expression of HLA class II molecules in humanized NOD.Rag1KO.IL2RgcKO mice is critical for development and function of human T and B cells. PLOS ONE 6:e19826
    [Google Scholar]
  22. De La Rochere P, Guil-Luna S, Decaudin D, Azar G, Sidhu SS, Piaggio E 2018. Humanized mice for the study of immuno-oncology. Trends Immunol 39:748–63
    [Google Scholar]
  23. Diaconu I, Ballard B, Zhang M, Chen Y, West J et al. 2017. Inducible caspase-9 selectively modulates the toxicities of CD19-specific chimeric antigen receptor-modified T cells. Mol. Ther. 25:580–92
    [Google Scholar]
  24. Ding Y, Wilkinson A, Idris A, Fancke B, O'Keeffe M et al. 2014. FLT3-ligand treatment of humanized mice results in the generation of large numbers of CD141+ and CD1c+ dendritic cells in vivo. J. Immunol. 192:1982–89
    [Google Scholar]
  25. Drake AC, Chen Q, Chen J 2012. Engineering humanized mice for improved hematopoietic reconstitution. Cell. Mol. Immunol. 9:215–24
    [Google Scholar]
  26. Dubrot J, Palazón A, Alfaro C, Azpilikueta A, Ochoa MC et al. 2011. Intratumoral injection of interferon-α and systemic delivery of agonist anti-CD137 monoclonal antibodies synergize for immunotherapy. Int. J. Cancer 128:105–18
    [Google Scholar]
  27. Durost PA, Aryee KE, Manzoor F, Tisch RM, Mueller C et al. 2018. Gene therapy with an adeno-associated viral vector expressing human interleukin-2 alters immune system homeostasis in humanized mice. Hum. Gene Ther. 29:352–65
    [Google Scholar]
  28. Einarsdottir BO, Karlsson J, Söderberg EMV, Lindberg MF, Funck-Brentano E et al. 2018. A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma. Cell Death Dis 9:810
    [Google Scholar]
  29. Fisher TS, Hooper AT, Lucas J, Clark TH, Rohner AK et al. 2018. A CD3-bispecific molecule targeting P-cadherin demonstrates T cell-mediated regression of established solid tumors in mice. Cancer Immunol. Immunother. 67:247–59
    [Google Scholar]
  30. Fisher TS, Kamperschroer C, Oliphant T, Love VA, Lira PD et al. 2012. Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity. Cancer Immunol. Immunother. 61:1721–33
    [Google Scholar]
  31. Forsberg EMV, Lindberg MF, Jespersen H, Alsen S, Bagge RO et al. 2019. HER2 CAR-T cells eradicate uveal melanoma and T-cell therapy-resistant human melanoma in IL2 transgenic NOD/SCID IL2 receptor knockout mice. Cancer Res 79:899–904
    [Google Scholar]
  32. Garris CS, Arlauckas SP, Kohler RH, Trefny MP, Garren S et al. 2018. Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12. Immunity 49:1148–61.e7
    [Google Scholar]
  33. Gellert M. 2002. V(D)J recombination: RAG proteins, repair factors, and regulation. Annu. Rev. Biochem. 71:101–32
    [Google Scholar]
  34. Genßler S, Burger MC, Zhang C, Oelsner S, Mildenberger I et al. 2016. Dual targeting of glioblastoma with chimeric antigen receptor-engineered natural killer cells overcomes heterogeneity of target antigen expression and enhances antitumor activity and survival. OncoImmunology 5:e1119354
    [Google Scholar]
  35. Giannoni F, Hardee CL, Wherley J, Gschweng E, Senadheera S et al. 2013. Allelic exclusion and peripheral reconstitution by TCR transgenic T cells arising from transduced human hematopoietic stem/progenitor cells. Mol. Ther. 21:1044–54
    [Google Scholar]
  36. Gille C, Orlikowsky TW, Spring B, Hartwig UF, Wilhelm A et al. 2012. Monocytes derived from humanized neonatal NOD/SCID/IL2Rγnull mice are phenotypically immature and exhibit functional impairments. Hum. Immunol. 73:346–54
    [Google Scholar]
  37. Gimeno R, Weijer K, Voordouw A, Uittenbogaart CH, Legrand N et al. 2004. Monitoring the effect of gene silencing by RNA interference in human CD34+ cells injected into newborn RAG2−/− γc−/− mice: functional inactivation of p53 in developing T cells. Blood 104:3886–93
    [Google Scholar]
  38. Glienke W, Esser R, Priesner C, Suerth JD, Schambach A et al. 2015. Advantages and applications of CAR-expressing natural killer cells. Front. Pharmacol. 6:21
    [Google Scholar]
  39. Greenblatt MB, Vbranac V, Tivey T, Tsang K, Tager AM, Aliprantis AO 2012. Graft versus host disease in the bone marrow, liver and thymus humanized mouse model. PLOS ONE 7:e44664
    [Google Scholar]
  40. Halkias J, Yen B, Taylor KT, Reinhartz O, Winoto A et al. 2015. Conserved and divergent aspects of human T-cell development and migration in humanized mice. Immunol. Cell Biol. 93:716–26
    [Google Scholar]
  41. Hanazawa A, Ito R, Katano I, Kawai K, Goto M et al. 2018. Generation of human immunosuppressive myeloid cell populations in human interleukin-6 transgenic NOG mice. Front. Immunol. 9:152
    [Google Scholar]
  42. Herndler-Brandstetter D, Shan L, Yao Y, Stecher C, Plajer V et al. 2017. Humanized mouse model supports development, function, and tissue residency of human natural killer cells. PNAS 114:E9626–34
    [Google Scholar]
  43. Ho Pyo K, Kim JH, Lee J-M, Kim SE, Cho JS et al. 2019. Promising preclinical platform for evaluation of immuno-oncology drugs using Hu-PBL-NSG lung cancer models. Lung Cancer 127:112–21
    [Google Scholar]
  44. Hu Z, Van Rooijen N, Yang YG 2011. Macrophages prevent human red blood cell reconstitution in immuno-deficient mice. Blood 118:5938–46
    [Google Scholar]
  45. Hu Z, Xia J, Fan W, Wargo J, Yang YG 2016. Human melanoma immunotherapy using tumor antigen-specific T cells generated in humanized mice. Oncotarget 7:6448–59
    [Google Scholar]
  46. Hu Z, Yang YG. 2012. Full reconstitution of human platelets in humanized mice after macrophage depletion. Blood 120:1713–16
    [Google Scholar]
  47. Huntington ND, Legrand N, Alves NL, Jaron B, Weijer K et al. 2009. IL-15 trans-presentation promotes human NK cell development and differentiation in vivo. J. Exp. Med. 206:25–34
    [Google Scholar]
  48. Ishiguro T, Sano Y, Komatsu SI, Kamata-Sakurai M, Kaneko A et al. 2017. An anti–glypican 3/CD3 bispecific T cell–redirecting antibody for treatment of solid tumors. Sci. Transl. Med. 9:eaaI4291
    [Google Scholar]
  49. Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M et al. 2002. NOD/SCID/γcnull mouse: an excellent recipient mouse model for engraftment of human cells. Blood 100:3175–82
    [Google Scholar]
  50. Ito R, Takahashi T, Katano I, Kawai K, Kamisako T et al. 2013. Establishment of a human allergy model using human IL-3/GM-CSF–transgenic NOG mice. J. Immunol. 191:2890–99
    [Google Scholar]
  51. Iwabuchi R, Ikeno S, Kobayashi-Ishihara M, Takeyama H, Ato M et al. 2018. Introduction of human Flt3-L and GM-CSF into humanized mice enhances the reconstitution and maturation of myeloid dendritic cells and the development of Foxp3+CD4+ T cells. Front. Immunol. 9:1042
    [Google Scholar]
  52. Jespersen H, Lindberg MF, Donia M, Söderberg EMV, Andersen R et al. 2017. Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model. Nat. Commun. 8:707
    [Google Scholar]
  53. Jin BY, Campbell TE, Draper LM, Stevanović S, Weissbrich B et al. 2018. Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model. JCI Insight 3:99488
    [Google Scholar]
  54. Jin CH, Xia J, Rafiq S, Huang X, Hu Z et al. 2019. Modeling anti-CD19 CAR T cell therapy in humanized mice with human immunity and autologous leukemia. EBioMedicine 39:173–81
    [Google Scholar]
  55. Johanna I, Straetemans T, Heijhuurs S, Aarts-Riemens T, Norell H et al. 2019. Evaluating in vivo efficacy—toxicity profile of TEG001 in humanized mice xenografts against primary human AML disease and healthy hematopoietic cells. J. Immunother. Cancer 7:69
    [Google Scholar]
  56. Ju C, Zhang M, Wu D, Tang J, Li S et al. 2019. Human interleukin 15 (IL15) humanized NCG mice support the human natural killer cells reconstitution and development. Blood 134:4871
    [Google Scholar]
  57. Junghans RP, Anderson CL. 1996. The protection receptor for IgG catabolism is the β2-microglobulin-containing neonatal intestinal transport receptor. PNAS 93:115512–16
    [Google Scholar]
  58. Katano I, Nishime C, Ito R, Kamisako T, Mizusawa T et al. 2017. Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse. Sci. Rep. 7:17230
    [Google Scholar]
  59. Katano I, Takahashi T, Ito R, Kamisako T, Mizusawa T et al. 2015. Predominant development of mature and functional human NK cells in a novel human IL-2-producing transgenic NOG mouse. J. Immunol. 194:3513–25
    [Google Scholar]
  60. Kaufman HL, Kohlhapp FJ, Zloza A 2015. Oncolytic viruses: a new class of immunotherapy drugs. Nat. Rev. Drug Discov. 14:642–62
    [Google Scholar]
  61. King M, Covassin L. 2009. Human peripheral blood leucocyte non‐obese diabetic‐severe combined immuno-deficiency interleukin‐2 receptor gamma chain gene mouse model of xenogeneic graft-versus-host-like disease and the role of host major histocompatibility complex. Clin. Exp. Immunol. 157:104–18
    [Google Scholar]
  62. Klichinsky M, Ruella M, Shestova O, Lu XM, Best A et al. 2020. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat. Biotechnol. 38:947–53
    [Google Scholar]
  63. Kuryk L, Møller A-SW, Jaderberg M 2018. Combination of immunogenic oncolytic adenovirus ONCOS-102 with anti-PD-1 pembrolizumab exhibits synergistic antitumor effect in humanized A2058 melanoma huNOG mouse model. OncoImmunology 8:e1532763
    [Google Scholar]
  64. Lavender KJ, Pace C, Sutter K, Messer RJ, Pouncey DL et al. 2018. An advanced BLT-humanized mouse model for extended HIV-1 cure studies. AIDS 32:1–10
    [Google Scholar]
  65. Li X, Lu P, Li B, Zhang W, Yang R et al. 2017. Interleukin 2 and interleukin 10 function synergistically to promote CD8+ T cell cytotoxicity, which is suppressed by regulatory T cells in breast cancer. Int. J. Biochem. Cell Biol. 87:1–7
    [Google Scholar]
  66. Lin S, Huang G, Cheng L, Li Z, Xiao Y et al. 2018. Establishment of peripheral blood mononuclear cell-derived humanized lung cancer mouse models for studying efficacy of PD-L1/PD-1 targeted immunotherapy. mAbs 10:1301–11
    [Google Scholar]
  67. Liu G, Fan X, Cai Y, Fu Z, Gao F et al. 2019. Efficacy of dendritic cell-based immunotherapy produced from cord blood in vitro and in a humanized NSG mouse cancer model. Immunotherapy 11:599–616
    [Google Scholar]
  68. Long BR, Stoddart CA. 2012. Alpha interferon and HIV infection cause activation of human T cells in NSG-BLT mice. J. Virol. 86:3327–36
    [Google Scholar]
  69. Majji S, Wijayalath W, Shashikumar S, Pow-Sang L, Villasante E et al. 2016. Differential effect of HLA class-I versus class-II transgenes on human T and B cell reconstitution and function in NRG mice. Sci. Rep. 6:28093
    [Google Scholar]
  70. Manz MG. 2007. Human-hemato-lymphoid-system mice: opportunities and challenges. Immunity 26:537–41
    [Google Scholar]
  71. Masse‐Ranson G, Dusséaux M, Fiquet O, Darche S, Boussand M et al. 2019. Accelerated thymopoiesis and improved T‐cell responses in HLA‐A2/‐DR2 transgenic BRGS‐based human immune system mice. Eur. J. Immunol. 49:6954–65
    [Google Scholar]
  72. McCune JM, Namikawa R, Kaneshima H, Shultz LD, Lieberman M, Weissman IL 1988. The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science 241:1632–39
    [Google Scholar]
  73. Meraz IM, Majidi M, Meng F, Shao R, Ha MJ et al. 2019. An improved patient-derived xenograft humanized mouse model for evaluation of lung cancer immune responses. Cancer Immunol. Res. 7:1267–79
    [Google Scholar]
  74. Miller PH, Rabu G, MacAldaz M, Knapp DJHF, Cheung AMS et al. 2017. Analysis of parameters that affect human hematopoietic cell outputs in mutant c-kit-immunodeficient mice. Exp. Hematol. 48:41–49
    [Google Scholar]
  75. Morton JJ, Bird G, Refaeli Y, Jimeno A 2016. Humanized mouse xenograft models: narrowing the tumor-microenvironment gap. Cancer Res 76:6153–58
    [Google Scholar]
  76. Mosier DE, Gulizia RJ, Baird SM, Wilson DB 1988. Transfer of a functional human immune system to mice with severe combined immunodeficiency. Nature 335:256–59
    [Google Scholar]
  77. Najima Y, Tomizawa-Murasawa M, Saito Y, Watanabe T, Ono R et al. 2016. Induction of WT1-specific human CD8+ T cells from human HSCs in HLA class I Tg NOD/SCID/IL2rgKO mice. Blood 127:722–34
    [Google Scholar]
  78. Newick K, O'Brien S, Moon E, Albelda SM 2017. CAR T cell therapy for solid tumors. Annu. Rev. Med. 68:139–52
    [Google Scholar]
  79. Nicolini FE, Cashman JD, Hogge DE, Humphries RK, Eaves CJ 2004. NOD/SCID mice engineered to express human IL-3, GM-CSF and Steel factor constitutively mobilize engrafted human progenitors and compromise human stem cell regeneration. Leukemia 18:341–47
    [Google Scholar]
  80. Ny L, Rizzo LY, Belgrano V, Karlsson J, Jespersen H et al. 2020. Supporting clinical decision making in advanced melanoma by preclinical testing in personalized immune-humanized xenograft mouse models. Ann. Oncol. 31:266–73
    [Google Scholar]
  81. Okada S, Vaeteewoottacharn K, Kariya R 2019. Application of highly immunocompromised mice for the establishment of patient-derived xenograft (PDX) models. Cells 8:889
    [Google Scholar]
  82. Perez CR, De Palma M 2019. Engineering dendritic cell vaccines to improve cancer immunotherapy. Nat. Commun. 10:5408
    [Google Scholar]
  83. Pérol L, Martin GH, Maury S, Cohen JL, Piaggio E 2014. Potential limitations of IL-2 administration for the treatment of experimental acute graft-versus-host disease. Immunol. Lett. 162:173–84
    [Google Scholar]
  84. Pizzitola I, Anjos-Afonso F, Rouault-Pierre K, Lassailly F, Tettamanti S et al. 2014. Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. Leukemia 28:1596–605
    [Google Scholar]
  85. Provasi E, Genovese P, Lombardo A, Magnani Z, Liu PQ et al. 2012. Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat. Med. 18:807–15
    [Google Scholar]
  86. Rahmig S, Kronstein-Wiedemann R, Fohgrub J, Kronstein N, Nevmerzhitskaya A et al. 2016. Improved human erythropoiesis and platelet formation in humanized NSGW41 mice. Stem Cell Rep 7:591–601
    [Google Scholar]
  87. Ranki T, Pesonen S, Hemminki A, Partanen K, Kairemo K et al. 2016. Phase I study with ONCOS-102 for the treatment of solid tumors: an evaluation of clinical response and exploratory analyses of immune markers. J. Immunother. Cancer 4:17
    [Google Scholar]
  88. Rius Ruiz I, Vicario R, Morancho B, Morales CB, Arenas EJ et al. 2018. p95HER2–T cell bispecific antibody for breast cancer treatment. Sci. Transl. Med. 10:eaat1445
    [Google Scholar]
  89. Rongvaux A, Takizawa H, Strowig T, Willinger T, Eynon EE et al. 2013. Human hemato-lymphoid system mice: current use and future potential for medicine. Annu. Rev. Immunol. 31:635–74
    [Google Scholar]
  90. Rongvaux A, Willinger T, Martinek J, Strowig T, Gearty SV et al. 2014. Development and function of human innate immune cells in a humanized mouse model. Nat Biotechnol 32:364–72
    [Google Scholar]
  91. Roopenian DC, Akilesh S. 2007. FcRn: The neonatal Fc receptor comes of age. Nat. Rev. Immunol. 7:715–25
    [Google Scholar]
  92. Rosenberg SA, Restifo NP. 2015. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 348:62–68
    [Google Scholar]
  93. Sanmamed MF, Rodriguez I, Schalper KA, Oñate C, Azpilikueta A et al. 2015. Nivolumab and urelumab enhance antitumor activity of human T lymphocytes engrafted in Rag2−/−IL2Rγnull immunodeficient mice. Cancer Res 75:3466–78
    [Google Scholar]
  94. Seidel D, Shibina A, Siebert N, Wels WS, Reynolds CP et al. 2015. Disialoganglioside-specific human natural killer cells are effective against drug-resistant neuroblastoma. Cancer Immunol. Immunother. 64:621–34
    [Google Scholar]
  95. Shultz LD, Ishikawa F, Greiner DL 2007. Humanized mice in translational biomedical research. Nat. Rev. Immunol. 7:118–30
    [Google Scholar]
  96. Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X et al. 2005. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2Rγnull mice engrafted with mobilized human hemopoietic stem cells. J. Immunol. 174:6477–89
    [Google Scholar]
  97. Shultz LD, Saito Y, Najima Y, Tanaka S, Ochi T et al. 2010. Generation of functional human T-cell subsets with HLA-restricted immune responses in HLA class I expressing NOD/SCID/IL2rγnull humanized mice. PNAS 107:13022–27
    [Google Scholar]
  98. Shultz LD, Schweitzer PA, Christianson SW, Gott B, Schweitzer IB et al. 1995. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. J. Immunol. 154:180–91
    [Google Scholar]
  99. Strowig T, Chijioke O, Carrega P, Arrey F, Meixlsperger S et al. 2010. Human NK cells of mice with reconstituted human immune system components require preactivation to acquire functional competence. Blood 116:4158–67
    [Google Scholar]
  100. Strowig T, Rongvaux A, Rathinam C, Takizawa H, Borsotti C et al. 2011. Transgenic expression of human signal regulatory protein alpha in Rag2−/−γc−/− mice improves engraftment of human hematopoietic cells in humanized mice. PNAS 108:13218–23
    [Google Scholar]
  101. Suzuki K, Hiramatsu H, Fukushima-Shintani M, Heike T, Nakahata T 2006. Efficient assay for evaluating human thrombopoiesis using NOD/SCID mice transplanted with cord blood CD34+ cells. Eur. J. Haematol. 78:123–30
    [Google Scholar]
  102. Suzuki M, Takahashi T, Katano I, Ito R, Ito M et al. 2012. Induction of human humoral immune responses in a novel HLA-DR-expressing transgenic NOD/Shi-scid/γcnull mouse. Int. Immunol. 24:243–52
    [Google Scholar]
  103. Takenaka K, Prasolava TK, Wang JCY, Mortin-Toth SM, Khalouei S et al. 2007. Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells. Nat. Immunol. 8:1313–23
    [Google Scholar]
  104. Tanaka S, Saito Y, Kunisawa J, Kurashima Y, Wake T et al. 2012. Development of mature and functional human myeloid subsets in hematopoietic stem cell-engrafted NOD/SCID/IL2rγKO mice. J. Immunol. 188:6145–55
    [Google Scholar]
  105. Theocharides APA, Rongvaux A, Fritsch K, Flavell RA, Manz MG 2016. Humanized hemato-lymphoid system mice. Haematologica 101:5–19
    [Google Scholar]
  106. Traggiai E, Chicha L, Mazzucchelli L, Bronz L, Piffaretti J-C et al. 2004. Development of a human adaptive immune system in cord blood cell-transplanted mice. Science 304:104–7
    [Google Scholar]
  107. Tsoneva D, Minev B, Frentzen A, Zhang Q, Wege AK, Szalay AA 2017. Humanized mice with subcutaneous human solid tumors for immune response analysis of vaccinia virus-mediated oncolysis. Mol. Ther. Oncolytics 5:41–61
    [Google Scholar]
  108. Van Der Lee DI, Reijmers RM, Honders MW, Hagedoorn RS, De Jong RCM et al. 2019. Mutated nucleophosmin 1 as immunotherapy target in acute myeloid leukemia. J. Clin. Investig. 129:774–85
    [Google Scholar]
  109. Vatakis DN, Bristol GC, Kim SG, Levin B, Liu W et al. 2012. Using the BLT humanized mouse as a stem cell based gene therapy tumor model. J. Vis. Exp. 18:4181
    [Google Scholar]
  110. Vatakis DN, Koya RC, Nixon CC, Wei L, Kim SG et al. 2011. Antitumor activity from antigen-specific CD8 T cells generated in vivo from genetically engineered human hematopoietic stem cells. PNAS 108:E1408
    [Google Scholar]
  111. Walsh NC, Kenney LL, Jangalwe S, Aryee K-E, Greiner DL et al. 2017. Humanized mouse models of clinical disease. Annu. Rev. Pathol. Mech. Dis. 12:187–215
    [Google Scholar]
  112. Watanabe K, Luo Y, Da T, Guedan S, Ruella M et al. 2018. Pancreatic cancer therapy with combined mesothelin-redirected chimeric antigen receptor T cells and cytokine-armed oncolytic adenoviruses. JCI Insight 3:99573
    [Google Scholar]
  113. Wege AK, Weber F, Kroemer A, Ortmann O, Nimmerjahn F, Brockhoff G 2017. IL-15 enhances the anti-tumor activity of trastuzumab against breast cancer cells but causes fatal side effects in humanized tumor mice (HTM). Oncotarget 8:2731–44
    [Google Scholar]
  114. Willinger T, Rongvaux A, Strowig T, Manz MG, Flavell RA 2011a. Improving human hemato-lymphoid-system mice by cytokine knock-in gene replacement. Trends Immunol 32:321–27
    [Google Scholar]
  115. Willinger T, Rongvaux A, Takizawa H, Yancopoulos GD, Valenzuela DM et al. 2011b. Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung. PNAS 108:2390–95
    [Google Scholar]
  116. Xiang Z, Liu Y, Zheng J, Liu M, Lv A et al. 2014. Targeted activation of human vγ9vδ2-T cells controls Epstein-Barr virus-induced B cell lymphoproliferative disease. Cancer Cell 26:565–76
    [Google Scholar]
  117. Xue W, Li W, Zhang T, Li Z, Wang Y et al. 2019. Anti-PD1 up-regulates PD-l1 expression and inhibits T-cell lymphoma progression: possible involvement of an IFN-γ-associated JAK-STAT pathway. OncoTargets Ther 12:2079–88
    [Google Scholar]
  118. Yaguchi T, Kobayashi A, Inozume T, Morii K, Nagumo H et al. 2018. Human PBMC-transferred murine MHC class I/II-deficient NOG mice enable long-term evaluation of human immune responses. Cell. Mol. Immunol. 15:953–62
    [Google Scholar]
  119. Yamauchi T, Takenaka K, Urata S, Shima T, Kikushige Y et al. 2013. Polymorphic Sirpa is the genetic determinant for NOD-based mouse lines to achieve efficient human cell engraftment. Blood 121:1316–25
    [Google Scholar]
  120. Yan H, Bhagwat B, Sanden D, Willingham A, Tan A et al. 2019. Evaluation of a TGN1412 analogue using in vitro assays and two immune humanized mouse models. Toxicol. Appl. Pharmacol. 372:57–69
    [Google Scholar]
  121. Yoshihara S, Li Y, Xia J, Danzl N, Sykes M, Yang YG 2019. Posttransplant hemophagocytic lymphohistiocytosis driven by myeloid cytokines and vicious cycles of T-cell and macrophage activation in humanized mice. Front. Immunol. 10:186
    [Google Scholar]
  122. Zafar S, Sorsa S, Siurala M, Hemminki O, Havunen R et al. 2018. CD40L coding oncolytic adenovirus allows long-term survival of humanized mice receiving dendritic cell therapy. OncoImmunology 7:e1490856
    [Google Scholar]
  123. Zeng Y, Liu B, Rubio M-TR, Wang X, Ojcius DM et al. 2017. Creation of an immunodeficient HLA-transgenic mouse (HUMAMICE) and functional validation of human immunity after transfer of HLA-matched human cells. PLOS ONE 12:e0173754
    [Google Scholar]
  124. Zhang X, Kim S, Hundal J, Herndon JM, Li S et al. 2017. Breast cancer neoantigens can induce CD8+ T-cell responses and antitumor immunity. Cancer Immunol. Res. 5:516–23
    [Google Scholar]
  125. Zumwalde NA, Sharma A, Xu X, Ma S, Schneider CL et al. 2017. Adoptively transferred Vγ9Vδ2 T cells show potent antitumor effects in a preclinical B cell lymphomagenesis model. JCI Insight 2:93179
    [Google Scholar]
/content/journals/10.1146/annurev-cancerbio-050520-100526
Loading
/content/journals/10.1146/annurev-cancerbio-050520-100526
Loading

Data & Media loading...

Supplementary Data

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error