References

oncotomsk

Сибирский онкологический журнал

Siberian journal of oncology

1814-48612312-3168

Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences

10.21294/1814-4861-2021-20-6-141-150

oncotomsk-1997

Research Article

ОБЗОРЫ

REVIEWS

Гуманизированные животные как модели экспериментальной онкологии (обзор литературы)

Humanized animals as models of experimental oncology (review)

https://orcid.org/0000-0003-3061-6108

Кит

О. И.

Kit

O. I.

доктор медицинских наук, профессор, член-корреспондент РАН, генеральный директор

SPIN-код: 1728-0329. Researcher ID (WOS): U-2241-2017. Author ID (Scopus): 55994103100

Россия, 344037, г. Ростов-на-Дону, 14 Линия, 63

MD, DSc, Professor, Corresponding Member of Russian Academy of Sciences, General Director

SPIN-код: 1728-0329. Researcher ID (WOS): U-2241-2017. Author ID (Scopus): 55994103100

63, 14 Line, 344037, Rostov-on-Don, Russia

Жукова

Г. В.

Zhukova

G. V.

доктор биологических наук, главный научный сотрудник

SPIN-код: 1887-7415. Researcher ID (WOS): Y-4243-2016. Author ID (Scopus): 7005456284

Россия, 344037, г. Ростов-на-Дону, 14 Линия, 63

DSc, Principal Investigator

SPIN-код: 1887-7415. Researcher ID (WOS): Y-4243-2016. Author ID (Scopus): 7005456284

63, 14 Line, 344037, Rostov-on-Don, Russia

galya_57@mail.ru

https://orcid.org/0000-0002-1397-837X

Максимов

А. Ю.

Maksimov

A. Yu.

доктор медицинских наук, профессор, заместитель генерального директора по перспективным научным разработкам

SPIN-код: 7322-5589. Author ID (Scopus): 56579049500

Россия, 344037, г. Ростов-на-Дону, 14 Линия, 63

MD, DSc, Professor, Deputy Director

SPIN-код: 7322-5589. Author ID (Scopus): 56579049500

63, 14 Line, 344037, Rostov-on-Don, Russia

https://orcid.org/0000-0003-0676-0871

Гончарова

А. С.

Goncharova

A. S.

кандидат биологических наук, руководитель

SPIN-код: 7512-2039

Россия, 344037, г. Ростов-на-Дону, 14 Линия, 63

PhD

SPIN-код: 7512-2039

63, 14 Line, 344037, Rostov-on-Don, Russia

Златник

Е. Ю.

Zlatnik

E. Yu.

доктор медицинских наук, профессор, главный научный сотрудник лаборатории иммунофенотипирования опухолей

SPIN-код: 4137-7410. Author ID (Scopus): 6603160432

Россия, 344037, г. Ростов-на-Дону, 14 Линия, 63

MD, Professor, Leading Researcher, Tumor Immunophenotyping Laboratory,

SPIN-код: 4137-7410. Author ID (Scopus): 6603160432

63, 14 Line, 344037, Rostov-on-Don, Russia

Новикова

И. А.

Novikova

I. A.

кандидат медицинских наук, заместитель генерального директора по науке

SPIN-код: 4810-2424. Researcher ID (WOS): E-7710-2018. Author ID (Scopus): 7005153343

Россия, 344037, г. Ростов-на-Дону, 14 Линия, 63

MD, PhD, Deputy Director for Science

SPIN-код: 4810-2424. Researcher ID (WOS): E-7710-2018. Author ID (Scopus): 7005153343

63, 14 Line, 344037, Rostov-on-Don, Russia

https://orcid.org/0000-0002-3036-6199

Лукбанова

Е. А.

Lukbanova

E. A.

младший научный сотрудник

SPIN-код: 4078-4200

Россия, 344037, г. Ростов-на-Дону, 14 Линия, 63

Junior Researcher

SPIN-код: 4078-4200

63, 14 Line, 344037, Rostov-on-Don, Russia

ФГБУ «Национальный медицинский исследовательский центр онкологии» Министерства здравоохранения Российской ФедерацииРоссияNational Medical Research Centre of OncologyRussian Federation

2021

13012022

206141150

2022

Кит О.И., Жукова Г.В., Максимов А.Ю., Гончарова А.С., Златник Е.Ю., Новикова И.А., Лукбанова Е.А.

Kit O.I., Zhukova G.V., Maksimov A.Y., Goncharova A.S., Zlatnik E.Y., Novikova I.A., Lukbanova E.A.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.siboncoj.ru/jour/article/view/1997

Гуманизация иммунодефицитных животных позволяет исследовать рост ксенотрансплантатов злокачественных опухолей человека и их реакцию на лечебные воздействия с учетом процессов в иммунной системе и зоне опухоли, оказывающих значительное влияние на онкогенез и эффективность противоопухолевой терапии. Такие экспериментальные модели в настоящее время рассматриваются в качестве наиболее совершенного инструмента при разработке персонализированного противоопухолевого лечения. В обзоре охарактеризованы линии иммунодефицитных животных, используемых для трансплантации зрелых и стволовых клеток иммунной системы человека, описаны основные источники получения иммунных клеток человека при реализации Hu-pBl и Hu-cd34+ моделей, обозначены основные процедуры, необходимые для воспроизведения каждой модели, их модификации у взрослых и новорожденных животных, а также параметры иммуносупрессивного лучевого воздействия, предваряющего трансплантацию гемопоэтических стволовых клеток человека. Описаны основные результаты гуманизации иммунодефицитных животных и примеры использования этих моделей для целей фундаментальной и клинической онкологии. Обсуждаются основные проблемы данного направления. Обзор составлен на основе анализа литературы, представленной в базах данных scopus, Web of science, medline, РИНЦ и др. за последние 7 лет (более 80 % источников, при этом более 50 % работ были опубликованы за последние 3 года).

The humanization of immunodeficient animals allows us to study the growth of xenografts of human malignant tumors and their response to therapeutic effects, taking into account processes in the immune system and tumor zone, which have a significant impact on oncogenesis and the effectiveness of antitumor therapy. Such experimental models are currently considered as the most advanced tool in the development of personalized antitumor treatment. The lines of immunodeficient animals most commonly used for the transplantation of mature and stem human immune cells have been characterized. The main sources of human immune cells when implementing the hu-pbl and hu-cd34+ models, as well as the blt model (as an option to the cd34+ model) are described. The basic procedures necessary for reproducing each model, their modification in adult and newborn animals are outlined as well as the parameters of immunosuppressive radiation exposure, preceding the transplantation of human hematopoietic stem cells. The main results of the humanization of immunodeficient animals and examples of the use of these models for the purposes of fundamental and clinical oncology are described. The main problems of this direction are discussed. The review is based on an analysis of the literature presented in the scopus, web of science, medline, risc and others databases over the past 7 years (over 80 % of literature sources, with more than over 50 % of studies published over the last 3 years).

ксенотрансплантаты злокачественных опухолей человекагуманизация иммунодефицитных животныхлейкоцитыгемопоэтические стволовые клеткисублетальное облучение

xenografts of human malignant tumorshumanization of immunodeficient animalswhite blood cellshematopoietic stem cellssublethal irradiation

References1

Williams J.A. Using PDX for Preclinical Cancer Drug Discovery: The Evolving Field. J Clin Med. 2018 Mar 2; 7(3): 41. doi: 10.3390/jcm7030041.

De La Rochere P., Guil-Luna S., Decaudin D., Azar G., Sidhu S.S., Piaggio E. Humanized Mice for the Study of Immuno-Oncology. Trends Immunol. 2018 Sep; 39(9): 748–763. doi: 10.1016/j.it.2018.07.001.

Wege A.K. Humanized Mouse Models for the Preclinical Assessment of Cancer Immunotherapy. BioDrugs. 2018; 32(3): 245–66. doi: 10.1007/s40259-018-0275-4.

Каркищенко Н.Н., Рябых В.П., Каркищенко В.Н., Колоскова Е.М. Создание гуманизированных мышей для фармакотоксикологических исследований (успехи, неудачи и перспективы). Биомедицина. 2014; (3): 4–22.

Karkischenko N.N., Ryabykh V.P., Karkishchenko V.N., Koloskova E.M. Creation of humanized mice for pharmacotoxicological research (successes, failures and prospects). Biomedicine. 2014; 3: 4–22. (in Russian).

Landgraf M., McGovern J.A., Friedl P., Hutmacher D.W. Rational Design of Mouse Models for Cancer Research. Trends Biotechnol. 2018 Mar; 36(3): 242–251. doi: 10.1016/j.tibtech.2017.12.001.

Zhou Q., Facciponte J., Jin M., Shen Q., Lin Q. Humanized NODSCID IL2rg–/– mice as a preclinical model for cancer research and its potential use for individualized cancer therapies. Cancer Lett. 2014 Mar 1; 344(1): 13–19. doi: 10.1016/j.canlet.2013.10.015.

Smith D.J., Lin L.J., Moon H., Pham A.T., Wang X., Liu S., Ji S., Rezek V., Shimizu S., Ruiz M., Lam J., Janzen D.M., Memarzadeh S., Kohn D.B., Zack J.A., Kitchen S.G., An D.S., Yang L. Propagating Humanized BLT Mice for the Study of Human Immunology and Immunotherapy. Stem Cells Dev. 2016 Dec 15; 25(24): 1863–1873. doi: 10.1089/scd.2016.0193.

Jespersen H., Lindberg M.F., Donia M., Söderberg E.M.V., Andersen R., Keller U., Ny L., Svane I.M., Nilsson L.M., Nilsson J.A. Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model. Nat Commun. 2017 Sep; 8(1): 707. doi: 10.1038/s41467-017-00786-z.

Murphy A.J., Macdonald L.E., Stevens S., Karow M., Dore A.T., Pobursky K., Huang T.T., Poueymirou W.T., Esau L., Meola M., Mikulka W., Krueger P., Fairhurst J., Valenzuela D.M., Papadopoulos N., Yancopoulos G.D. Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice. Proc Natl Acad Sci U S A. 2014 Apr 8; 111(14): 5153–8. doi: 10.1073/pnas.1324022111.

Kersten K., de Visser K.E., van Miltenburg M.H., Jonkers J. Genetically engineered mouse models in oncology research and cancer medicine. EMBO Mol Med. 2017 Feb; 9(2): 137–153. doi: 10.15252/emmm.201606857.

Холоденко И.В., Доронин И.И., Холоденко Р.В. Опухолевые модели в изучении онкологических заболеваний. Иммунология. 2013; 5: 282–286.

Kholodenko I.V., Doronin I.I., Kholodenko R.V. Tumor models in the study of cancer diseases. Immunology. 2013; 5: 282–286. (in Russian).

Céspedes M.V., Casanova I., Parreño M., Mangues R. Mouse models in oncogenesis and cancer therapy. Clin Transl Oncol. 2006 May; 8(5): 318–29. doi: 10.1007/s12094-006-0177-7.

Medler T.R., Cotechini T., Coussens L.M. Immune response to cancer therapy: mounting an effective antitumor response and mechanisms of resistance. Trends Cancer. 2015 Sep 1; 1(1): 66–75. doi: 10.1016/j.trecan.2015.07.008.

Zhukova G.V., Shikhliarova A.I., Soldatov A.V., Barteneva T.A., Petrosian V.I., Gudtskova T.N., Bragina M.I., Polozhentsev O.E., Sheiko E.A., Maschenko N.M., Shirnina E.A., Zlatnik E.Y., Kurkina T.A. Some Approaches to Activation of Antitumor Resistance Mechanisms and Functional Analogs in Categories of Synergetics. Biofizika. 2016 MarApr; 61(2): 359–73.

Morton J.J., Bird G., Refaeli Y., Jimeno A. Humanized Mouse Xenograft Models: Narrowing the Tumor-Microenvironment Gap. Cancer Res. 2016 Nov 1; 76(21): 6153–6158. doi: 10.1158/0008-5472.CAN-16-1260.

Morton J.J., Bird G., Refaeli Y., Jimeno A. Humanized Mouse Xenograft Models: Narrowing the Tumor-Microenvironment Gap. Cancer Res. 2016; 76(21): 6153–6158. doi: 10.1158/0008-5472.CAN-16-1260.

Bracci L., Schiavoni G., Sistigu A., Belardelli F. Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer. Cell Death Differ. 2014 Jan; 21(1): 15–25. doi: 10.1038/cdd.2013.67.

Kähkönen T.E., Suominen M.I., Halleen J.M., Haapaniemi T., Tanaka A., Seiler M., Bernoulli J. Humanized mouse models of triplenegative and triple-positive breast cancer for preclinical validation of novel immuno-oncology therapies. Eur J Cancer. 2018; 92: S7‒S8. doi: 10.1016/j.ejca.2018.01.020.

Scadden D., Silberstein L. Hematology: Basic Principles and Practice, Chapter 11, 119-12 Hematopoietic Microenvironment. 7 Ed. Elsevier, 2018. 2408 p.

Holzapfel B.M., Thibaudeau L., Hesami P. Humanised xenograft models of bone metastasis revisited: novel insights into species-specific mechanisms of cancer cell osteotropism. Cancer Metastasis Rev. 2013; 32: 129–135. doi: 10.1007/s10555-013-9437-5.

Bosma G.C., Custer R.P., Bosma M.J. A severe combined immunodeficiency mutation in the mouse. Nature. 1983 Feb 10; 301(5900): 527–30. doi: 10.1038/301527a0.

Xie X., Brünner N., Jensen G., Albrectsen J., Gotthardsen B., Rygaard J. Comparative studies between nude and scid mice on the growth and metastatic behavior of xenografted human tumors. Clin Exp Metastasis. 1992 May; 10(3): 201–10. doi: 10.1007/BF00132752.

Shultz L.D., Ishikawa F., Greiner D.L. Humanized mice in translational biomedical research. Nat Rev Immunol. 2007 Feb; 7(2): 118–30. doi: 10.1038/nri2017.

Ito M., Hiramatsu H., Kobayashi K., Suzue K., Kawahata M., Hioki K., Ueyama Y., Koyanagi Y., Sugamura K., Tsuji K., Heike T., Nakahata T. NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood. 2002 Nov 1; 100(9): 3175–82. doi: 10.1182/blood-2001-12-0207.

Панков Д.Д., Румянцев А.Г. Оптимизация экспериментальных моделей заболевания лейкозом у человека (обзор литературы). Онкогематология. 2012; (4): 48–52.doi: 10.17650/1818-8346-2012-7-4-48-52.

Pankov D.D.1., Rumyantsev A.G. Optimization of experimental human leukemia models (review). Oncohematology. 2012; (4): 48–52. (in Russian). doi: 10.17650/1818-8346-2012-7-4-48-52.

Pearson T., Greiner D.L., Shultz L.D. Creation of «humanized» mice to study human immunity. Curr Protoc Immunol. 2008 May; Chapter 15: Unit 15.21. doi: 10.1002/0471142735.im1521s81.

Трещалина Е.М. Иммунодефицитные мыши balb/c nude и моделирование различных вариантов опухолевого роста для доклинических исследований. Российский биотерапевтический журнал. 2017; 16(3): 6–13. doi: 10.17650/1726-9784-2017-16-3-6-13.

Treshalina H.M. Immunodeficient mice balb/c nude and modeling of various types of tumor growth for preclinical studies. Russian Journal of Biotherapy. 2017; 16(3): 6–13. (in Russian). doi: 10.17650/1726-9784-2017-16-3-6-13.

Pompili L., Porru M., Caruso C., Biroccio A., Leonetti C. Patientderived xenografts: a relevant preclinical model for drug development. J Exp Clin Cancer Res. 2016; 35: 189. doi: 10.1186/s13046-016-0462-4.

Chen P., Huang Y., Womer K.L. Effects of mesenchymal stromal cells on human myeloid dendritic cell differentiation and maturation in a humanized mouse model. J Immunol Methods. 2015 Dec; 427: 100–4. doi: 10.1016/j.jim.2015.10.008.

DeRose Y.S., Wang G., Lin Y.C., Bernard P.S., Buys S.S., Ebbert M.T., Factor R., Matsen C., Milash B.A., Nelson E., Neumayer L., Randall R.L., Stijleman I.J., Welm B.E., Welm A.L. Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nat Med. 2011 Oct; 17(11): 1514–20. doi: 10.1038/nm.2454.

Moser J., van Ark J., van Dijk M.C., Greiner D.L., Shultz L.D., van Goor H., Hillebrands J.L. Distinct Differences on Neointima Formation in Immunodeficient and Humanized Mice after Carotid or Femoral Arterial Injury. Sci Rep. 2016 Oct 19; 6: 35387. doi: 10.1038/srep35387.

Sanmamed M.F., Rodriguez I., Schalper K.A., Oñate C., Azpilikueta A., Rodriguez-Ruiz M.E., Morales-Kastresana A., Labiano S., Pérez-Gracia J.L., Martín-Algarra S., Alfaro C., Mazzolini G., Sarno F., Hidalgo M., Korman A.J., Jure-Kunkel M., Melero I. Nivolumab and Urelumab Enhance Antitumor Activity of Human T Lymphocytes Engrafted in Rag2-/-IL2Rγnull Immunodeficient Mice. Cancer Res. 2015 Sep 1; 75(17): 3466–78. doi: 10.1158/0008-5472.CAN-14-3510.

Chang D.K., Moniz R.J., Xu Z., Sun J., Signoretti S., Zhu Q., Marasco W.A. Human anti-CAIX antibodies mediate immune cell inhibition of renal cell carcinoma in vitro and in a humanized mouse model in vivo. Mol Cancer. 2015 Jun 11; 14: 119. doi: 10.1186/s12943-015-0384-3.

Roth M.D., Harui A. Human tumor infiltrating lymphocytes cooperatively regulate prostate tumor growth in a humanized mouse model. J Immunother Cancer. 2015 Apr 21; 3: 12. doi: 10.1186/s40425-015-0056-2.

Ye W., Jiang Z., Li G.X., Xiao Y., Lin S., Lai Y., Wang S., Li B., Jia B., Li Y., Huang Z.L., Li J, Feng F., Li S., Yao H., Liu Z., Cao S., Xu L., Li Y., Wu D., Zeng L, Zhong M., Liu P., Wen Z.S., Xu B., Yao Y., Pei D., Li P. Quantitative evaluation of the immunodeficiency of a mouse strain by tumor engraftments. J Hematol Oncol. 2015 May 29; 8: 59. doi: 10.1186/s13045-015-0156-y.

Choi Y., Lee S., Kim K., Kim S.H., Chung Y.J., Lee C. Studying cancer immunotherapy using patient-derived xenografts (PDXs) in humanized mice. Exp Mol Med. 2018 Aug 7; 50(8): 1–9. doi: 10.1038/s12276-018-0115-0.

Naserian S., Leclerc M., Thiolat A., Pilon C., Le Bret C., Belkacemi Y., Maury S., Charlotte F., Cohen J.L. Simple, Reproducible, and Efficient Clinical Grading System for Murine Models of Acute Graftversus-Host Disease. Front Immunol. 2018 Jan 22; 9: 10. doi: 10.3389/fimmu.2018.00010.

Ishikawa F., Yasukawa M., Lyons B., Yoshida S., Miyamoto T., Yoshimoto G., Watanabe T., Akashi K., Shultz L.D., Harada M. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice. Blood. 2005; 106(5): 1565–73. doi: 10.1182/blood-2005-02-0516.

Knibbe-Hollinger J.S., Fields N.R., Chaudoin T.R., Epstein A.A., Makarov E., Akhter S.P., Gorantla S., Bonasera S.J., Gendelman H.E., Poluektova L.Y. Influence of age, irradiation and humanization on NSG mouse phenotypes. Biol Open. 2015 Sep 9; 4(10): 1243–52. doi: 10.1242/bio.013201.

Miller P.H., Rabu G., MacAldaz M., Knapp D.J., Cheung A.M., Dhillon K., Nakamichi N., Beer P.A., Shultz L.D., Humphries R.K., Eaves C.J. Analysis of parameters that affect human hematopoietic cell outputs in mutant c-kit-immunodeficient mice. Exp Hematol. 2017 Apr; 48: 41–49. doi: 10.1016/j.exphem.2016.12.012.

Brehm M.A., Bortell R., Diiorio P., Leif J., Laning J., Cuthbert A., Yang C., Herlihy M., Burzenski L., Gott B., Foreman O., Powers A.C., Greiner D.L., Shultz L.D. Human immune system development and rejection of human islet allografts in spontaneously diabetic NOD-Rag1null IL2rgammanull Ins2Akita mice. Diabetes. 2010 Sep; 59(9): 2265–70. doi: 10.2337/db10-0323.

Morton J.J., Bird G., Keysar S.B., Astling D.P., Lyons T.R., Anderson R.T., Glogowska M.J., Estes P., Eagles J.R., Le P.N., Gan G., McGettigan B., Fernandez P., Padilla-Just N., Varella-Garcia M., Song J.I., Bowles D.W., Schedin P., Tan A.C., Roop D.R., Wang X.J., Refaeli Y., Jimeno A. XactMice: humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer. Oncogene. 2016 Jan 21; 35(3): 290–300. doi: 10.1038/onc.2015.94.

Tsoneva D., Minev B., Frentzen A., Zhang Q., Wege A.K., Szalay A.A. Humanized Mice with Subcutaneous Human Solid Tumors for Immune Response Analysis of Vaccinia Virus-Mediated Oncolysis. Mol Ther Oncolytics. 2017 Mar 21; 5: 41–61. doi: 10.1016/j.omto.2017.03.001.

Xia J., Hu Z., Yoshihara S., Li Y., Jin C.H., Tan S., Li W., Chen Q., Sykes M., Yang Y.G. Modeling Human Leukemia Immunotherapy in Humanized Mice. EBioMedicine. 2016 Aug; 10: 101–8. doi: 10.1016/j.ebiom.2016.06.028.

Brehm M.A., Wiles M.V., Greiner D.L., Shultz L.D. Generation of improved humanized mouse models for human infectious diseases. J Immunol Methods. 2014 Aug; 410: 3–17. doi: 10.1016/j.jim.2014.02.011.

Klevorn L.E., Teague R.M. Adapting Cancer Immunotherapy Models for the Real World. Trends Immunol. 2016 Jun; 37(6): 354–363. doi: 10.1016/j.it.2016.03.010.

Abarrategi A., Mian S.A., Passaro D., Rouault-Pierre K., Grey W., Bonnet D. Modeling the human bone marrow niche in mice: From host bone marrow engraftment to bioengineering approaches. J Exp Med. 2018 Mar 5; 215(3): 729–743. doi: 10.1084/jem.20172139.

Rahmig S., Kronstein-Wiedemann R., Fohgrub J., Kronstein N., Nevmerzhitskaya A., Bornhäuser M., Gassmann M., Platz A., Ordemann R., Tonn T., Waskow C. Improved Human Erythropoiesis and Platelet Formation in Humanized NSGW41 Mice. Stem Cell Reports. 2016 Oct 11; 7(4): 591–601. doi: 10.1016/j.stemcr.2016.08.005.

Katano I., Nishime C., Ito R, Kamisako T., Mizusawa T., Ka Y., Ogura T., Suemizu H., Kawakami Y., Ito M., Takahashi T. Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15-transgenic NOG mouse. Sci Rep. 2017; 7(1): 17230. doi: 10.1038/s41598-017-17442-7.

Herndler-Brandstetter D., Shan L., Yao Y., Stecher C., Plajer V., Lietzenmayer M., Strowig T., de Zoete M.R., Palm N.W., Chen J., Blish C.A., Frleta D., Gurer C., Macdonald L.E., Murphy A.J., Yancopoulos G.D., Montgomery R.R., Flavell R.A. Humanized mouse model supports development, function, and tissue residency of human natural killer cells. Proc Natl Acad Sci USA. 2017 Nov 7; 114(45): E9626–E9634. doi: 10.1073/pnas.1705301114.

Zeng Y., Liu B., Rubio M.T., Wang X., Ojcius D.M., Tang R., Durrbach A., Ru Z., Zhou Y., Lone Y.C. Creation of an immunodeficient HLA-transgenic mouse (HUMAMICE) and functional validation of human immunity after transfer of HLA-matched human cells. PLoS One. 2017 Apr 11; 12(4): e0173754. doi: 10.1371/journal.pone.0173754.

Huszthy P.C., Sakariassen P.Ø., Espedal H., Brokstad K.A., Bjerkvig R., Miletic H. Engraftment of Human Glioblastoma Cells in Immunocompetent Rats through Acquired Immunosuppression. PLoS One. 2015 Aug 20; 10(8): e0136089. doi: 10.1371/journal.pone.0136089.

Semenkow S., Li S., Kahlert U.D., Raabe E.H., Xu J., Arnold A., Janowski M., Oh B.C., Brandacher G., Bulte J.W.M., Eberhart C.G., Walczak P. An immunocompetent mouse model of human glioblastoma. Oncotarget. 2017 May 15; 8(37): 61072–61082. doi: 10.18632/oncotarget.17851.

The authors declare that there are no conflicts of interest present.