НЕКОТОРЫЕ АСПЕКТЫ ИСПОЛЬЗОВАНИЯ АЛЛО- И КСЕНОГРАФТНЫХ МОДЕЛЕЙ ПРИ РАЗРАБОТКЕ ПРОТИВОРАКОВЫХ ВАКЦИН И ОНКОЛИТИЧЕСКИХ ВИРУСОВ

На настоящий момент онкологические заболевания являются одной из основных причин смертности и заболеваемости у населения. Последние достижения в области изучения молекулярно-генетических механизмов онкогенеза и иммунного ответа организма открывают широкие возможности для создания новых эффективных средств борьбы с неопластическими заболеваниями, более специфичных к опухолевым клеткам и менее токсичных для организма. Одними из наиболее многообещающих подходов являются иммунотерапевтические противораковые вакцины и онколитические вирусы. Для проведения быстрого и надежного скрининга и доклинического тестирования необходимо использование релевантных животных моделей. Такие модели обеспечивают возможность воспроизвести микроокружение и васкуляризацию опухоли, а также, в некоторой мере, воздействие иммунной системы. Наиболее активно в исследованиях раковых заболеваний используются аллографтные и ксенографтные опухолевые модели. Аллогенная трансплантация предполагает перенос раковых клеток или фрагментов опухоли от одного организма к другому организму того же вида. Ксенопластическая трансплантация предполагает перенос опухолевых клеток или тканей между организмами, относящимися к разным биологическим видам. Для ксенотрансплантации могут быть использованы как клеточные линии, так и клетки опухоли, полученные от пациентов в результате биопсии. За последние несколько десятилетий исследователям удалось разработать целый ряд линий иммунодефицитных мышей и крыс, пригодных для использования в качестве моделей человеческих опухолей. Однако несмотря на достигнутые успехи такие модели имеют существенные ограничения, связанные с невозможностью полностью воспроизвести микроокружение опухоли, реконструировать функциональную иммунную систему человека у мышей, а также с развитием реакции отторжения трансплантата. Таким образом при планировании экспериментов необходим тщательный анализ и критическое рассмотрение достоинств и недостатков различных линий животных, используемых в экспериментальной онкологии.

рак, иммунные ответ, иммунотерапия, онколитические вирусы, противораковые вакцины, аллографтные модели, ксенографтные модели, лабораторные животные

1. Augusto D.G. The Impact of KIR Polymorphism on the Risk of Developing Cancer: Not as Strong as Imagined? Frontiers in Genetics, 2016, Vol. 7, no.121. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923111/ [DOI:10.3389/fgene.2016.00121]

2. Bankert R.B., Balu-Iyer S.V., Odunsi K., Shultz L.D., Kelleher R.J.Jr, Barnas J.L., Simpson-Abelson M., Parsons R., Yokota S.J. Humanized mouse model of ovarian cancer recapitulates patient solid tumor progression, ascites formation, and metastasis. PLoS One, 2011, Vol. 6, no. 9, pp. e24420. URL: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0024420 [DOI:10.1371/journal.pone.0024420]

3. Bankert R.B., Hess S.D., Egilmez N.K. SCID mouse models to study human cancer pathogenesis and approaches to therapy: potential, limitations, and future directions. Frontiers in Bioscience, 2002, Vol. 7, pp. 44-62. URL: http://www.bioscience.org/2002/v7/c/bankert/fulltext.php?bframe=2.htm

4. Bollard J., Couderc C., Blanc M., Poncet G., Lepinasse F., Hervieu V., Gouysse G., Ferraropeyret C., Benslama N., Walter T., Scoazec J.Y., Roche C. Antitumor effect of everolimus in preclinical models of high-grade gastroenteropancreatic neuroendocrine carcinomas. Neuroendocrinology, 2013, Vol. 97, pp. 331-340. URL: https://www.karger.com/Article/Abstract/347063 [DOI: 10.1159/000347063]

5. Buonaguro L., Petrizzo A., Tornesello M.L., Buonaguro F.M. Translating tumor antigens into cancer vaccines. Clinical and Vaccine Immunology, 2011, Vol. 18, no. 1, pp. 23–34. URL: http://cvi.asm.org/content/18/1/23.full [DOI:10.1128/CVI.00286-10]

6. Butterfield L.H. Lessons learned from cancer vaccine trials and target antigen choice. Cancer Immunology, Immunotherapy, 2016, Vol. 65, no. 7, pp. 805-812. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919159/ [DOI:10.1007/s00262-016-1801-1]

7. Cadili A., Kneteman N. The role of macrophages in xenograft rejection. Transplantation Proceedings, 2008, Vol. 40, pp. 3289-3293. URL: https://www.ncbi.nlm.nih.gov/pubmed/19100374 [DOI:10.1016/j.transproceed.2008.08.125]

8. Cassidy J.W., Caldas C., Bruna A. Maintaining Tumor Heterogeneity in Patient-Derived Tumor Xenografts. Cancer Research, 2015, Vol. 75, no. 15, pp. 2963-2968. URL: http://cancerres.aacrjournals.org/content/75/15/2963 [DOI:10.1158/0008-5472.CAN-15-0727]

9. 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. Molecular Cancer, 2015, Vol. 14, pp. 119. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464115/ [DOI:10.1186/s12943-015-0384-3]

10. Chester C., Ambulkar S., Kohrt H.E. 4-1BB agonism: adding the accelerator to cancer immunotherapy. Cancer Immunology, Immunotherapy, 2016, Vol. 65, no. 10, pp. 1243-1248. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035667/ [DOI:10.1007/s00262-016-1829-2]

11. Cho S.Y., Kang W., Han J.Y., Min S., Kang J., Lee A., Kwon J.Y., Lee C., Park H. An Integrative Approach to Precision Cancer Medicine Using Patient-Derived Xenografts. Molecules and Cells, 2016, Vol. 39, no. 2, pp. 77-86. URL: http://www.molcells.org/journal/view.html?doi=10.14348/molcells.2016.2350 [DOI:10.14348/molcells.2016.2350]

12. Coulie P.G., Van den Eynde B.J., van der Bruggen P., Boon T. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nature Reviews Cancer, 2014, Vol. 14, no. 2, pp. 135-146. URL: https://www.nature.com/articles/nrc3670 [DOI:10.1038/nrc3670]

13. Decker W.K., da Silva R.F., Sanabria M.H., Angelo L.S., Guimarães F., Burt B.M., Kheradmand F., Paust S. Cancer Immunotherapy: Historical Perspective of a Clinical Revolution and Emerging Preclinical Animal Models. Frontiers in Immunology, 2017, Vol. 8, pp. 829. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539135/ [DOI:10.3389/fimmu.2017.00829]

14. Defosse D.L., Duray P.H., Johnson R.C. The NIH-3 immunodeficient mouse is a model for Lyme borreliosis myositis and carditis. The American Journal of Pathology, 1992, Vol. 141, no. 1, pp. 3. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1886584/

15. DeRose Y.S., Wang G., Lin Y.-C., Bernard P.S., Buys S.S., Ebbert M.T.W., 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. Nature Medicine, 2011, Vol. 17, pp. 1514-1520. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3553601/ [DOI:10.1038/nm.2454]

16. Dipersio L.P. Regional growth differences of human tumour xenografts in nude mice. Laboratory Animals, 1981, Vol. 15, pp. 179-180. URL: http://journals.sagepub.com/doi/abs/10.1258/002367781780959044 [DOI:10.1258/002367781780959044]

17. Flanagan S.P. ‘Nude’, a new hairless gene with pleiotropic effects in the mouse. Genetics Research, 1966, Vol. 8, pp. 295-309. URL: https://www.ncbi.nlm.nih.gov/pubmed/5980117 [DOI:10.1017/S0016672300010168]

18. Fogh J., Fogh J.M., Orfeo T. One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. Journal of the National Cancer Institute, 1977, Vol. 59, pp. 221-226. URL: https://www.ncbi.nlm.nih.gov/pubmed/327080

19. Froidevaux S., Loor F. A quick procedure for identifying doubly homozygous immunodeficient scid beige mice. Journal of Immunological Methods, 1991, Vol. 137, no. 2, pp. 275-279. URL: https://www.sciencedirect.com/science/article/pii/002217599190034D [DOI:10.1016/0022-1759(91)90034-D]

20. Garber K. China approves world's first oncolytic virus therapy for cancer treatment. Journal of the National Cancer Institute, 2006, Vol. 98, pp. 298-300. URL: https://academic.oup.com/jnci/article/98/5/298/2522047 [DOI:10.1093/jnci/djj111]

21. Giovanella B.C., Fogh J. The nude mouse in cancer research. Advances in Cancer Research, 1985, Vol. 44, pp. 69-120. URL: https://doi.org/10.1016/S0065-230X(08)60026-3 [DOI:10.1016/S0065-230X(08)60026-3]

22. Gotoh K., Kariya R., Matsuda K., Hattori S., Vaeteewoottacharn K., Okada S. A novel EGFP-expressing nude mice with complete loss of lymphocytes and NK cells to study tumor-host interactions. Bioscience trends, 2014, Vol. 8, no. 4, pp. 202-205. URL: https://www.jstage.jst.go.jp/article/bst/8/4/8_2014.01049/_article [DOI:10.5582/bst.2014.01049]

23. Grakoui A., Bromley S.K., Sumen C., Davis M.M., Shaw A.S., Allen P.M., Dustin M.L. The immunological synapse: a molecular machine controlling T cell activation. Science, 1999, Vol. 285, no. 5425, pp. 221-227. URL: http://science.sciencemag.org/content/285/5425/221.long [DOI:10.1126/science.285.5425.221]

24. Greco A., Albanese S., Auletta L., Mirabelli P., Zannetti A., D’alterio C., Di Maro G., Orlandella F.M., Salvatore G., Soricelli A., Salvatore M. High-frequency ultrasound-guided injection for the generation of a novel orthotopic mouse model of human thyroid carcinoma. Thyroid, 2016, Vol. 26, pp. 552-558. URL: https://www.ncbi.nlm.nih.gov/pubmed/26844598 [DOI:10.1089/thy.2015.0511]

25. Hao Z., Rajewsky K. Homeostasis of peripheral B cells in the absence of B cell influx from the bone marrow. Journal of Experimental Medicine, 2001, Vol. 194, no. 8, pp. 1151-1164. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193512/ [DOI:10.1084/jem.194.8.1151]

26. He L., Tian D.-A., Li P.-Y., He X.-X. Mouse models of liver cancer: progress and recommendations. Oncotarget, 2015, Vol. 6, pp. 23306-23322. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695120/ [DOI:10.18632/oncotarget.4202]

27. Hidalgo M., Amant F., Biankin A.V., Budinska E., Byrne A.T., Caldas C., Clarke R.B., de Jong S., Jonkers J., Maelandsmo G.M., Roman-Roman S., Seoane J., Trusolino L., Villanueva A. Patient-derived xenograft models: an emerging platform for translational cancer research. Cancer Discovery, 2014, Vol. 4, pp. 998-1013. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4167608/ [DOI:10.1158/2159-8290.CD-14-0001]

28. Hoffman R.M. Orthotopic metastatic mouse models for anticancer drug discovery and evaluation: a bridge to the clinic. Investigational New Drugs, 1999, Vol. 17, pp. 343-359. URL: http://www.metamouse.com/RMH-1999.IND.pdf

29. Holay N., Kim Y., Lee P., Gujar S. Sharpening the Edge for Precision Cancer Immunotherapy: Targeting Tumor Antigens through Oncolytic Vaccines. Frontiers in immunology, 2017, Vol. 8, pp. 800. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507961/ [DOI:10.3389/fimmu.2017.00800]

30. Holen I., Speirs V., Morrissey B., Blyth K. In vivo models in breast cancer research: progress, challenges and future directions. Disease Models and Mechanisms, 2017, Vol. 1;10, no. 4, pp. 359-371. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399571/ [DOI:10.1242/dmm.028274]

31. Holub M. The nude mouse. ILAR Jornal, 1992, Vol. 34, pp. 1-3. URL: https://academic.oup.com/ilarjournal/article/34/1-2/1/685936 [DOI:10.1093/ilar.34.1-2.1]

32. Kaufman H.L., Kohlhapp F.J., Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nature Reviews Drug Discovery, 2015, Vol. 14, no. 9, pp. 642–662. URL: https://www.nature.com/articles/nrd4663 [DOI:10.1038/nrd4663]

33. Khanna C., Hunter K. Modeling metastasis in vivo. Carcinogenesis, 2005, Vol. 26, pp. 513-523. URL: https://academic.oup.com/carcin/article/26/3/513/2390765 [DOI:10.1093/carcin/bgh261]

34. Killion J.J., Radinsky R., Fidler I.J. Orthotopic models are necessary to predict therapy of transplantable tumors in mice. Cancer and Metastasis Reviews, 1998, Vol. 17, pp. 279-284. URL: https://link.springer.com/article/10.1023%2FA%3A1006140513233 [DOI:10.1023/A:1006140513233]

35. Kinter A.L., Godbout E.J., McNally J.P., Sereti I., Roby G.A., O'Shea M.A., Fauci A.S. The common gamma-chain cytokines IL-2, IL-7, IL-15, and IL-21 induce the expression of programmed death-1 and its ligands. Journal of Immunology, 2008, Vol. 181, no. 10, pp. 6738-6746. URL: http://www.jimmunol.org/content/181/10/6738.long [DOI:10.4049/jimmunol.181.10.6738]

36. Klebanoff C.A., Acquavella N., Yu Z., Restifo N.P. Therapeutic cancer vaccines: are we there yet? Immunological Reviews, 2011, Vol. 239, no. 1, pp. 27-44. URL: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1600-065X.2010.00979.x [DOI:10.1111/j.1600-065X.2010.00979.x]

37. Kudrin A., Hanna Jr M.G. Overview of the cancer vaccine field: are we moving forward? Human vaccines & immunotherapeutics, 2012, Vol. 8, no. 8, pp. 1135-1140. URL: https://www.tandfonline.com/doi/abs/10.4161/hv.20474 [DOI:10.4161/hv.20474]

38. Lang J., Weiss N., Freed B.M., Torres R.M., Pelanda R. Generation of hematopoietic humanized mice in the newborn BALB/c-Rag2 null Il2rγ null mouse model: a multivariable optimization approach. Clinical Immunology, 2011, Vol. 140, no. 1, pp. 102-116. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115423/ [DOI:10.1016/j.clim.2011.04.002]

39. Liu Z., Sun Y., Hong H., Zhao S., Zou X., Ma R., Jiang C., Wang Z., Li H., Liu H. 3-bromopyruvate enhanced daunorubicin-induced cytotoxicity involved in monocarboxylate transporter 1 in breast cancer cells. American Journal of Cancer Research, 2015, Vol. 5, pp. 2673-2685. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633897/

40. Mansfield D.C., Kyula J.N., Rosenfelder N., Chao-Chu J., Kramer-Marek G., Khan A.A., Roulstone V., McLaughlin M., Melcher A.A., Vile R.G., Pandha H.S., Khoo V., Harrington K.J. Oncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer. Gene Therapy, 2016, Vol. 23, no. 4, pp. 357-368. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827015/ [DOI:10.1038/gt.2016.5]

41. Marangoni E., Vincent-Salomon A., Auger N., Degeorges A., Assayag F., de Cremoux P., de Plater L., Guyader C., De Pinieux G., Judde J.-G., Rebucci M., Tran-Perennou C., Sastre-Garau X., Sigal-Zafrani B., Delattre O., Diéras V., Poupon M.F. A new model of patient tumor-derived breast cancer xenografts for preclinical assays. Clinical Cancer Research, 2007, Vol. 13, pp. 3989-3998. URL: http://clincancerres.aacrjournals.org/content/13/13/3989.long [DOI:10.1158/1078-0432.CCR-07-0078]

42. Mecklenburg L., Tychsen B., Paus R. Learning from nudity: lessons from the nude phenotype. Experimental Dermatology, 2005, Vol. 14, pp. 797-810. URL: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1600-0625.2005.00362.x [DOI:10.1111/j.1600-0625.2005.00362.x]

43. Melcher A., Parato K., Rooney C.M., Bell J.C. Thunder and lightning: immunotherapy and oncolytic viruses collide. Molecular Therapy, 2011, Vol. 19, no. 6, pp. 1008–1016. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129809/ [DOI:10.1038/mt.2011.65]

44. Mombaerts P., Iacomini J., Johnson R.S., Herrup K., Tonegawa S., Papaioannou V.E. RAG-1-deficient mice have no mature B and T lymphocytes. Cell, 1992, Vol. 68, no. 5, pp. 869-877. URL: https://www.ncbi.nlm.nih.gov/pubmed/1547488

45. Moore J.C., Langenau D.M. Allograft Cancer Cell Transplantation in Zebrafish. Advances in Experimental Medicine and Biology, 2016, Vol. 916, pp. 265-287. URL: https://link.springer.com/chapter/10.1007%2F978-3-319-30654-4_12 [DOI:10.1007/978-3-319-30654-4_12]

46. Morton J.J., Bird G., Refaeli Y., Jimeno A. Humanized Mouse Xenograft Models: Narrowing the Tumor-Microenvironment Gap. Cancer Research, 2016, Vol. 76, no. 21, pp. 6153-6158. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093075/ [DOI:10.1158/0008-5472.CAN-16-1260]

47. Neefjes J., Ovaa H. A peptide’s perspective on antigen presentation to the immune system. Nature Chemical Biology, 2013, Vol. 9, no. 12, pp. 769–75. URL: https://www.nature.com/articles/nchembio.1391 [DOI:10.1038/nchembio.1391]

48. Nölting S., Giubellino A., Tayem Y., Young K., Lauseker M., Bullova P., Schovanek J., Anver M., Fliedner S., Korbonits M., Göke B., Vlotides G., Grossman A., Pacak K. Combination of 13-Cis retinoic acid and lovastatin: marked antitumor potential in vivo in a pheochromocytoma allograft model in female athymic nude mice. Endocrinology, 2014, Vol. 155, pp. 2377-2390. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060189/ [DOI:10.1210/en.2014-1027]

49. Pacak K., Sirova M., Giubellino A., Lencesova L., Csaderova L., Hudecova S., Krizanova O. NF-κB inhibition significantly upregulates the norepinephrine transporter system, causes apoptosis in pheochromocytoma cell lines and prevents metastasis in an animal model. International Journal of Cancer, 2012, Vol. 131, pp. 2445-2455. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131300/ [DOI:10.1002/ijc.27524]

50. Pantelouris E.M. Athymic development in the mouse. Differentiation, 1973, Vol. 1, pp. 437-450. URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1432-0436.1973.tb00143.x [DOI:10.1111/j.1432-0436.1973.tb00143.x]

51. Parato K.A., Senger D., Forsyth P.A.J., Bell J.C. Recent progress in the battle between oncolytic viruses and tumours. Nature Reviews Cancer, 2005, Vol. 5, no. 12, pp. 965-976. URL: https://www.nature.com/articles/nrc1750 [DOI:10.1038/nrc1750]

52. Prochazka M.I.C.H.A.L., Gaskins H.R., Shultz L.D., Leiter E.H. The nonobese diabetic scid mouse: model for spontaneous thymomagenesis associated with immunodeficiency. Proceedings of the National Academy of Sciences, 1992, Vol. 89, no. 8, pp. 3290-3294. URL: http://www.pnas.org/content/89/8/3290 [DOI:10.1073/pnas.89.8.3290]

53. Prowse D.M., Lee D., Weiner L., Jiang N., Magro C.M., Baden H.P., Brissette J.L. Ectopic expression of the nude gene induces hyperproliferation and defects in differentiation: implications for the self-renewal of cutaneous epithelia. Developmental Biology, 1999, Vol. 212, pp. 54-67. URL: https://www.sciencedirect.com/science/article/pii/S0012160699993284 [DOI:10.1006/dbio.1999.9328]

54. Rahal O.M., Nie L., Chan L.-C., Li C.-W., Hsu Y.-H., Hsu J., Yu D., Hung M.-C. Selective expression of constitutively active pro-apoptotic protein BikDD gene in primary mammary tumors inhibits tumor growth and reduces tumor initiating cells. American Journal of Cancer Research, 2015, Vol. 5, pp. 3624-3634. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731636/

55. Richmond A., Su Y. Mouse xenograft models vs GEM models for human cancer therapeutics. Disease Models and Mechanisms, 2008, Vol. 1, no. 2-3, pp. 78-82. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562196/ [DOI:10.1242/dmm.000976]

56. Romano R., Palamaro L., Fusco A., Iannace L., Maio S., Vigliano I., Giardino G., Pignata C. From murine to human nude/SCID: the thymus, T-cell development and the missing link. Clinical and Developmental Immunology, 2012, Vol. 2012, no. 467101. URL: https://www.hindawi.com/journals/jir/2012/467101/ [DOI:10.1155/2012/467101]

57. Roth M.D., Harui A. Human tumor infiltrating lymphocytes cooperatively regulate prostate tumor growth in a humanized mouse model. Journal for Immunotherapy of Cancer, 2015, Vol. 3, pp. 12. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404579/ [DOI:10.1186/s40425-015-0056-2]

58. Ruiz P., Maldonado P., Hidalgo Y., Gleisner A., Sauma D., Silva C., Saez J.J., Nuñez S., Rosemblatt M., Bono M.R. Transplant tolerance: new insights and strategies for long-term allograft acceptance. Clinical and Developmental Immunology, 2013, Vol. 2013, pp. 210506. URL: https://www.hindawi.com/journals/jir/2013/210506/ [DOI:10.1155/2013/210506]

59. Sanmamed M.F., Pastor F., Rodriguez A., Perez-Gracia J.L., Rodriguez-Ruiz M.E., Jure-Kunkel M., Melero I. Agonists of Co-stimulation in Cancer Immunotherapy Directed Against CD137, OX40, GITR, CD27, CD28, and ICOS. Seminars in Oncology, 2015, Vol. 42, no. 4, pp. 640-655. URL: https://www.seminoncol.org/article/S0093-7754(15)00112-8 [DOI:10.1053/j.seminoncol.2015.05.014]

60. Saxena M., Christofori G. Rebuilding cancer metastasis in the mouse. Molecular Oncology, 2013, Vol. 7, pp. 283-296. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528417/ [DOI:10.1016/j.molonc.2013.02.009]

61. Schuh J.C.L. Trials, tribulations, and trends in tumor modeling in mice. Toxicologic Pathology, 2004, Vol. 32, pp. 53-66. URL: http://journals.sagepub.com/doi/abs/10.1080/01926230490424770 [DOI:10.1080/01926230490424770]

62. Scott C.L., Mackay H.J., Haluska P. Patient-derived xenograft models in gynecological malignancies. American Society of Clinical Oncology Educational Book, 2014, Vol. 3, pp. e258-e266. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156101/ [DOI:10.14694/EdBook_AM.2014.34.e258]

63. Shultz L.D., Brehm M.A., Garcia-Martinez J.V., Greiner D.L. Humanized mice for immune system investigation: progress, promise and challenges. Nature Reviews Immunology, 2012, Vol. 12, pp. 786-798. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749872/ [DOI:10.1038/nri3311]

64. Shultz L.D., Goodwin N., Ishikawa F., Hosur V., Lyons B.L., Greiner D.L. Human cancer growth and therapy in NOD/SCID/IL2Rγnull (NSG) mice. Cold Spring Harbor Protocols, 2014, Vol. 2014, pp. 694-708. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411952/ [DOI:10.1101/pdb.top073585]

65. Shultz L.D., Ishikawa F., Greiner D.L. Humanized mice in translational biomedical research. Nature Reviews Immunology, 2007, Vol. 7, no. 2, pp. 118-130. URL: https://www.nature.com/articles/nri2017 [DOI:10.1038/nri2017]

66. Shultz L.D., Lang P.A., Christianson S.W., Gott B., Lyons B., Umeda S., Leiter E., Hesselton R., Wagar E.J., Leif J.H., Kollet O., Lapidot T., Greiner D.L. NOD/LtSz-Rag1null mice: an immunodeficient and human hematolymphoid cells, HIV infection, and adoptive transfer of NOD mouse diabetogenic T cells. Journal of Immunology, 2000, Vol. 164, pp. 2496-2507. URL: http://www.jimmunol.org/content/164/5/2496.long [DOI:10.4049/jimmunol.164.5.2496]

67. Simmons J.K., Hildreth B.E., Supsavhad W., Elshafae S.M., Hassan B.B., Dirksen W.P., Toribio R.E., Rosol T.J. Animal models of bone metastasis. Veterenary Pathology, 2015, Vol. 52, pp. 827-841. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545712/ [DOI:10.1177/0300985815586223]

68. Simpson-Abelson M.R., Sonnenberg G.F., Takita H., Yokota S.J., Conway T.F. Jr., Kelleher R.J.Jr., Shultz L.D., Barcos M., Bankert R.B. Long-term engraftment and expansion of tumor-derived memory T cells following the implantation of non-disrupted pieces of human lung tumor into NOD-scid IL2Rgamma(null) mice. Journal of Immunology, 2008, Vol. 180, no. 10, pp. 7009-7018. URL: http://www.jimmunol.org/content/180/10/7009.long [DOI:10.4049/jimmunol.180.10.7009]

69. Siolas D., Hannon G.J. Patient-derived tumor xenografts: transforming clinical samples into mouse models. Cancer Research, 2013, Vol. 73, no. 17, pp. 5315-5319. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766500/ [DOI:10.1158/0008-5472.CAN-13-1069]

70. Srinivasan R., Wolchok J.D. Tumor antigens for cancer immunotherapy: therapeutic potential of xenogeneic DNA vaccines. Journal of Translational Medicine, 2004, Vol. 2, no. 1, pp. 12. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC419720/ [DOI:10.1186/1479-5876-2-12]

71. Stakleff K.D.S., Von Gruenigen V.E. Rodent models for ovarian cancer research. International Journal of Gynecological Cancer, 2003, Vol. 13, pp. 405-412. URL: https://journals.lww.com/ijgc/Fulltext/2003/07000/Rodent_models_for_ovarian_cancer_research.2.aspx

72. Sun L., Li H., Luo H., Zhao Y. Thymic epithelial cell development and its dysfunction in human diseases. Biomed Research International, 2014, Vol. 2014, pp. 206929. URL: https://www.hindawi.com/journals/bmri/2014/206929/ [DOI:10.1155/2014/206929]

73. Szadvari I., Krizanova O., Babula P. Athymic nude mice as an experimental model for cancer treatment. Physiological Research, 2016, Vol. 65 (S. 4), pp. S441-S453. URL: http://www.biomed.cas.cz/physiolres/pdf/65/65_S441.pdf

74. Tentler J.J., Tan A.C., Weekes C.D., Jimeno A., Leong S., Pitts T.M., Arcaroli J.J., Messersmith W.A., Eckhardt S.G. Patient-derived tumour xenografts as models for oncology drug development. Nature Reviews Clinical Oncology, 2012, Vol. 9, pp. 338-350. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3928688/ [DOI:10.1038/nrclinonc.2012.61]

75. Thomas F.T., Marchman W., Carobbi A., DeMasi R., Araneda D., Patselas T., Larkin E., Pittman K., Alqaisi M., Haisch C., Thomas J.M. Immunobiology of xenografting in rodents. In Cooper D.K.C., Kemp E., Reemtsma K., White D.J.G. (eds) Xenotransplantation. Springer, Berlin, Heidelberg, 1991, pp. 139-160. URL: https://link.springer.com/chapter/10.1007/978-3-642-97323-9_9 [DOI:10.1007/978-3-642-97323-9_9]

76. Tomayko M.M., Reynolds C.P. Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemotherapy and Pharmacology, 1989, Vol. 24, pp. 148-154. URL: https://link.springer.com/article/10.1007/BF00300234 [DOI:10.1007/BF00300234]

77. Workman P., Aboagye E.O., Balkwill F., Balmain A., Bruder G., Chaplin D.J., Double J.A., Everitt J., Farningham D.A., Glennie M.J., Kelland L.R., Robinson V., Stratford I.J., Tozer G.M., Watson S., Wedge S.R., Eccles S.A. Guidelines for the welfare and use of animals in cancer research. British Journal of Cancer, 2010, Vol. 102, pp. 1555-1577. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883160/ [DOI:10.1038/sj.bjc.6605642]

78. Xiong Y., Kotian S., Zeiger M.A., Zhang L., Kebebew E. miR-126-3p inhibits thyroid cancer cell growth and metastasis, and is associated with aggressive thyroid cancer. PloS One, 2015, Vol. 10, pp. e0130496. URL: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130496 [DOI: 10.1371/journal.pone.0130496]