Name: testing cancer immunotherapeutics in a humanized mouse model bearing human tumors
Uploaded: 2022-12-16T13:50:00
Description: Watch this Scientific Journal Video about Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors at JoVE.com

我们要感谢动物研究机构（OLAR）对我们小鼠的照顾，以及我们研究所癌症中心支持补助金（P30CA046934）支持的流式细胞术共享资源，感谢他们对我们所有工作的巨大帮助。我们还感谢Gail Eckhardt和Anna Capasso在我们的HIS-BRGS模型中研究人类PDX免疫疗法的首次合作。这项研究得到了美国国立卫生研究院P30CA06934癌症中心支持基金的部分支持，并使用PHISM（临床前人类免疫系统小鼠模型）共享资源，RRID：SCR_021990和流式细胞术共享资源，RRID：SCR_022035。这项研究得到了美国国立卫生研究院NIAID的部分支持，合同号为75N93020C00058。

所有动物工作均根据科罗拉多大学丹佛分校机构动物护理和使用委员会批准的动物协议（IACUC 协议 #00593 和 #00021）进行。所有动物工作均按照科罗拉多大学丹佛安舒茨医学院的美国实验动物护理协会认可的设施实验动物资源办公室 （OLAR） 进行。所有人类脐带血样本都是从去识别化的捐赠者那里获得的，因此无需人类研究伦理委员会的批准。
注意：协议中提到的所有介质和?...

<ol>
	<li>Chulpanova, D. S., Kitaeva, K. V., Rutland, C. S., Rizvanov, A. A., Solovyeva, V. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+tumor+models+for+advanced+cancer+immunotherapy.">Mouse tumor models for advanced cancer immunotherapy.</a> International Journal of Molecular Sciences. 21 (11), 4118 (2020).</li><li>Olson, B., Li, Y., Lin, Y., Liu, E. T., Patnaik, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mouse+models+for+cancer+immunotherapy+research.">Mouse models for cancer immunotherapy research.</a> Cancer Discovery. 8 (11), 1358-1365 (2018).</li><li>Marin-Jimenez, J. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Testing+cancer+immunotherapy+in+a+human+immune+system+mouse+model:+correlating+treatment+responses+to+human+chimerism,+therapeutic+variables+and+immune+cell+phenotypes.">Testing cancer immunotherapy in a human immune system mouse model: correlating treatment responses to human chimerism, therapeutic variables and immune cell phenotypes.</a> Frontiers in Immunology. 12, 607282 (2021).</li><li>Yin, L., Wang, X. J., Chen, D. X., Liu, X. N., Wang, X. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Humanized+mouse+model:+a+review+on+preclinical+applications+for+cancer+immunotherapy.">Humanized mouse model: a review on preclinical applications for cancer immunotherapy.</a> American Journal of Cancer Research. 10 (12), 4568-4584 (2020).</li><li>Cogels, M. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Humanized+mice+as+a+valuable+pre-clinical+model+for+cancer+immunotherapy+research.">Humanized mice as a valuable pre-clinical model for cancer immunotherapy research.</a> Frontiers in Oncology. 11, 784947 (2021).</li><li>Jin, K. T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+humanized+mouse+with+patient-derived+xenografts+for+cancer+immunotherapy+studies:+A+comprehensive+review.">Development of humanized mouse with patient-derived xenografts for cancer immunotherapy studies: A comprehensive review.</a> Cancer Science. 112 (7), 2592-2606 (2021).</li><li>Capasso, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+immune+responses+to+anti-PD-1+mono+and+combination+immunotherapy+in+hematopoietic+humanized+mice+implanted+with+tumor+xenografts.">Characterization of immune responses to anti-PD-1 mono and combination immunotherapy in hematopoietic humanized mice implanted with tumor xenografts.</a> Journal for Immunotherapy of Cancer. 7 (1), 37 (2019).</li><li>Wang, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Humanized+mice+in+studying+efficacy+and+mechanisms+of+PD-1-targeted+cancer+immunotherapy.">Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy.</a> The FASEB Journal. 32 (3), 1537-1549 (2018).</li><li>Yong, K. S. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Humanized+mouse+as+a+tool+to+predict+immunotoxicity+of+human+biologics.">Humanized mouse as a tool to predict immunotoxicity of human biologics.</a> Frontiers in Immunology. 11, 553362 (2020).</li><li>Shen, H. W., Jiang, X. L., Gonzalez, F. J., Yu, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Humanized+transgenic+mouse+models+for+drug+metabolism+and+pharmacokinetic+research.">Humanized transgenic mouse models for drug metabolism and pharmacokinetic research.</a> Current Drug Metabolism. 12 (10), 997-1006 (2011).</li><li>Bosma, G. C., Custer, R. P., Bosma, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+severe+combined+immunodeficiency+mutation+in+the+mouse.">A severe combined immunodeficiency mutation in the mouse.</a> Nature. 301 (5900), 527-530 (1983).</li><li>Shultz, L. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multiple+defects+in+innate+and+adaptive+immunologic+function+in+NOD/LtSz-scid+mice.">Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice.</a> The Journal of Immunology. 154 (1), 180-191 (1995).</li><li>Legrand, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+CD47/signal+regulatory+protein+alpha+(SIRP(alpha))+interaction+is+required+for+optimal+human+T-+and+natural+killer-+(NK)+cell+homeostasis+in+vivo.">Functional CD47/signal regulatory protein alpha (SIRP(alpha)) interaction is required for optimal human T- and natural killer- (NK) cell homeostasis in vivo.</a> Proceedings of the National Academy of Sciences. 108 (32), 13224-13229 (2011).</li><li>Ishikawa, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+functional+human+blood+and+immune+systems+in+NOD/SCID/IL2+receptor+{gamma}+chain(null)+mice.">Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice.</a> Blood. 106 (5), 1565-1573 (2005).</li><li>Ito, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=NOD/SCID/gamma(c)(null)+mouse:+an+excellent+recipient+mouse+model+for+engraftment+of+human+cells.">NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells.</a> Blood. 100 (9), 3175-3182 (2002).</li><li>Shultz, L. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+lymphoid+and+myeloid+cell+development+in+NOD/LtSz-scid+IL2R+gamma+null+mice+engrafted+with+mobilized+human+hemopoietic+stem+cells.">Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells.</a> The Journal of Immunology. 174 (10), 6477-6489 (2005).</li><li>Traggiai, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+a+human+adaptive+immune+system+in+cord+blood+cell-transplanted+mice.">Development of a human adaptive immune system in cord blood cell-transplanted mice.</a> Science. 304 (5667), 104-107 (2004).</li><li>Theocharides, A. P., Rongvaux, A., Fritsch, K., Flavell, R. A., Manz, M. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Humanized+hemato-lymphoid+system+mice.">Humanized hemato-lymphoid system mice.</a> Haematologica. 101 (1), 5-19 (2016).</li><li>Goldman, J. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Enhanced+human+cell+engraftment+in+mice+deficient+in+RAG2+and+the+common+cytokine+receptor+gamma+chain.">Enhanced human cell engraftment in mice deficient in RAG2 and the common cytokine receptor gamma chain.</a> British Journal of Haematology. 103 (2), 335-342 (1998).</li><li>Stripecke, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Innovations,+challenges,+and+minimal+information+for+standardization+of+humanized+mice.">Innovations, challenges, and minimal information for standardization of humanized mice.</a> EMBO Molecular Medicine. 12 (7), (2020).</li><li>Allen, T. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Humanized+immune+system+mouse+models:+progress,+challenges+and+opportunities.">Humanized immune system mouse models: progress, challenges and opportunities.</a> Nature Immunology. 20 (7), 770-774 (2019).</li><li>Gammelgaard, O. L., Terp, M. G., Preiss, B., Ditzel, H. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+cancer+evolution+in+the+context+of+a+human+immune+system+in+mice.">Human cancer evolution in the context of a human immune system in mice.</a> Molecular Oncology. 12 (10), 1797-1810 (2018).</li><li>Rios-Doria, J., Stevens, C., Maddage, C., Lasky, K., Koblish, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+human+cancer+xenografts+in+humanized+mice.">Characterization of human cancer xenografts in humanized mice.</a> Journal for Immunotherapy of Cancer. 8 (1), 000416 (2020).</li><li>Gombash Lampe, S. E., Kaspar, B. K., Foust, K. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intravenous+injections+in+neonatal+mice.">Intravenous injections in neonatal mice.</a> Journal of Visualized Experiments. (93), e52037 (2014).</li><li>Lang, J., Weiss, N., Freed, B. M., Torres, R. M., Pelanda, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Generation+of+hematopoietic+humanized+mice+in+the+newborn+BALB/c-Rag2null+Il2r&#947;null+mouse+model:+a+multivariable+optimization+approach.">Generation of hematopoietic humanized mice in the newborn BALB/c-Rag2null Il2r&#947;null mouse model: a multivariable optimization approach.</a> Clinical Immunology. 140 (1), 102-116 (2011).</li><li>Laskowski, T. J., Hazen, A. L., Collazo, R. S., Haviland, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rigor+and+reproducibility+of+cytometry+practices+for+immuno-oncology:+a+multifaceted+challenge.">Rigor and reproducibility of cytometry practices for immuno-oncology: a multifaceted challenge.</a> Cytometry Part A. 97 (2), 116-125 (2020).</li><li>Bagby, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+and+maintenance+of+a+preclinical+patient+derived+tumor+xenograft+model+for+the+investigation+of+novel+anti-cancer+therapies.">Development and maintenance of a preclinical patient derived tumor xenograft model for the investigation of novel anti-cancer therapies.</a> Journal of Visualized Experiments. (115), e54393 (2016).</li><li>Laajala, T. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimized+design+and+analysis+of+preclinical+intervention+studies+in+vivo.">Optimized design and analysis of preclinical intervention studies in vivo.</a> Scientific Reports. 6, 30723 (2016).</li><li>Na, Y. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Establishment+of+patient-derived+xenografts+from+patients+with+gastrointestinal+stromal+tumors:+analysis+of+clinicopathological+characteristics+related+to+engraftment+success.">Establishment of patient-derived xenografts from patients with gastrointestinal stromal tumors: analysis of clinicopathological characteristics related to engraftment success.</a> Scientific Reports. 10 (1), 7996 (2020).</li><li>Tentler, J. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=RX-5902,+a+novel+beta-catenin+modulator,+potentiates+the+efficacy+of+immune+checkpoint+inhibitors+in+preclinical+models+of+triple-negative+breast+cancer.">RX-5902, a novel beta-catenin modulator, potentiates the efficacy of immune checkpoint inhibitors in preclinical models of triple-negative breast cancer.</a> BMC Cancer. 20 (1), 1063 (2020).</li><li>Lang, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+an+adrenocortical+cancer+humanized+mouse+model+to+characterize+anti-PD1+effects+on+tumor+microenvironment.">Development of an adrenocortical cancer humanized mouse model to characterize anti-PD1 effects on tumor microenvironment.</a> The Journal of Clinical Endocrinology &amp; Metabolism. 105 (1), 26-42 (2020).</li><li>Lang, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Studies+of+lymphocyte+reconstitution+in+a+humanized+mouse+model+reveal+a+requirement+of+T+cells+for+human+B+cell+maturation.">Studies of lymphocyte reconstitution in a humanized mouse model reveal a requirement of T cells for human B cell maturation.</a> The Journal of Immunology. 190 (5), 2090-2101 (2013).</li><li>Katano, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=NOD-Rag2null+IL-2R&#947;null+mice:+an+alternative+to+NOG+mice+for+generation+of+humanized+mice.">NOD-Rag2null IL-2R&#947;null mice: an alternative to NOG mice for generation of humanized mice.</a> Experimental Animalas. 63 (3), 321-330 (2014).</li><li>Brehm, M. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Parameters+for+establishing+humanized+mouse+models+to+study+human+immunity:+analysis+of+human+hematopoietic+stem+cell+engraftment+in+three+immunodeficient+strains+of+mice+bearing+the+IL2r&#947;(null)+mutation.">Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2r&#947;(null) mutation.</a> Clinical Immunology. 135 (1), 84-98 (2010).</li><li>Hasgur, S., Aryee, K. E., Shultz, L. D., Greiner, D. L., Brehm, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Generation+of+immunodeficient+mice+bearing+human+immune+systems+by+the+engraftment+of+hematopoietic+stem+cells.">Generation of immunodeficient mice bearing human immune systems by the engraftment of hematopoietic stem cells.</a> Methods in Molecular Biology. 1438, 67-78 (2016).</li><li>Andre, M. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+human+CD34++stem+cell-engrafted+nonobese+diabetic/SCID/IL-2R&#947;null+mice+show+impaired+CD8++T+cell+maintenance+and+a+functional+arrest+of+immature+NK+cells.">Long-term human CD34+ stem cell-engrafted nonobese diabetic/SCID/IL-2R&#947;null mice show impaired CD8+ T cell maintenance and a functional arrest of immature NK cells.</a> The Journal of Immunology. 185 (5), 2710-2720 (2010).</li><li>Wunderlich, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improved+multilineage+human+hematopoietic+reconstitution+and+function+in+NSGS+mice.">Improved multilineage human hematopoietic reconstitution and function in NSGS mice.</a> PLoS One. 13 (12), 0209034 (2018).</li><li>Lee, J., Brehm, M. A., Greiner, D., Shultz, L. D., Kornfeld, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Engrafted+human+cells+generate+adaptive+immune+responses+to+Mycobacterium+bovis+BCG+infection+in+humanized+mice.">Engrafted human cells generate adaptive immune responses to Mycobacterium bovis BCG infection in humanized mice.</a> BMC Immunology. 14, 53 (2013).</li><li>Masse-Ranson, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Accelerated+thymopoiesis+and+improved+T-cell+responses+in+HLA-A2/-DR2+transgenic+BRGS-based+human+immune+system+mice.">Accelerated thymopoiesis and improved T-cell responses in HLA-A2/-DR2 transgenic BRGS-based human immune system mice.</a> European Journal of Immunology. 49 (6), 954-965 (2019).</li><li>Oswald, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Immune+cell+infiltration+pattern+in+non-small+cell+lung+cancer+PDX+models+is+a+model+immanent+feature+and+correlates+with+a+distinct+molecular+and+phenotypic+make-up.">Immune cell infiltration pattern in non-small cell lung cancer PDX models is a model immanent feature and correlates with a distinct molecular and phenotypic make-up.</a> Journal for Immunotherapy of Cancer. 10 (4), 004412 (2022).</li></ol>

在过去的6年中，利用我们在免疫学和人源化小鼠方面的专业知识，我们的研究团队开发了一个急需的临床前模型来测试免疫疗法对各种人类肿瘤3，7，30，31。该协议强调考虑模型的可变性，特别关注以免疫治疗为中心的人类T细胞群。在该协议中，描述了HIS小鼠的产生，以及其淋巴器官和肿瘤的免疫?...

An erratum was issued for:&#160;<a href="https://www.jove.com/t/64606">Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors</a>. The Authors section was updated from:
Jordi M. Lanis1 
Matthew S. Lewis1 
Hannah Strassburger1 
Stacey M. Bagby2 
Adrian T. A. Dominguez2 
Juan A. Mar&#237;n-Jim&#233;nez3 
Roberta Pelanda1 
Todd M. Pitts2 
Julie Lang1 
1Department of Immunology and Microbiology, School of Medicine, University of Colorado Denver Anschutz Medical Campus 
2Division of Oncology, School of Medicine, University of Colorado Denver Anschutz Medical Campus 
3Department of Medical Oncology, Catalan Institute of Oncology (ICO-L&#8217;Hospitalet)
to:
Jordi M. Lanis1 
Matthew S. Lewis1 
Hannah Strassburger1 
Kristina Larsen1 
Stacey M. Bagby2 
Adrian T. A. Dominguez2 
Juan A. Mar&#237;n-Jim&#233;nez3 
Roberta Pelanda1 
Todd M. Pitts2 
Julie Lang1 
1Department of Immunology and Microbiology, School of Medicine, University of Colorado Denver Anschutz Medical Campus 
2Division of Oncology, School of Medicine, University of Colorado Denver Anschutz Medical Campus 
3Department of Medical Oncology, Catalan Institute of Oncology (ICO-L&#8217;Hospitalet)

An erratum was issued for:&#160;<a href="https://www.jove.com/t/64606">Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors</a>. The Authors section was updated.

Erratum: Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors

小鼠癌症模型对于建立肿瘤生长和免疫逃逸的基本机制很重要。然而，由于有限的同系模型和物种特异性差异，小鼠模型中的癌症治疗研究已经产生了有限的临床翻译1，2。免疫疗法作为控制肿瘤的主要方法的出现重申了对具有功能性人类免疫系统的体内模型的需求。在过去的十年中，人类免疫系统小鼠（HIS小鼠）的进步使得在各种癌症类型和免疫治疗剂中研究体内免疫肿瘤学成为可能3，4，5，6。人类肿瘤模型，包括细胞系衍生和患者来源的异种移植物（分别为CDX和PDX），在HIS小鼠中生长良好，并且在大多数情况下与它们在缺乏人类造血植入的免疫缺陷宿主中的生长几乎相同7，8。基于这一关键发现，研究人员一直在使用HIS小鼠模型来研究人类免疫疗法，包括旨在改变肿瘤微环境（TME）以减少免疫抑制从而增强免疫定向肿瘤杀伤的联合疗法。这些临床前模型有助于解决人类癌症的异质性问题，还可以预测治疗成功以及监测免疫相关药物毒性9，10。
通过引入人造血干细胞来生产具有人类免疫系统的小鼠模型需要不会排斥异种移植物的受体免疫缺陷小鼠。目前的HIS小鼠模型来源于30多年前报道的免疫缺陷小鼠品系。描述的第一个免疫缺陷小鼠品系是缺乏T细胞和B细胞的SCID小鼠11，其次是具有SIRPα多态性的杂交NOD-SCID，负责小鼠巨噬细胞对人类细胞的耐受性，这是由于NOD SIRPα等位基因与人CD47分子12，13的结合增加。在 2000 年代初期，由于基因缺失禁止宿主 NK 细胞发育，ALLB/c 和 NOD 免疫缺陷菌株上 IL-2 受体 （IL-2Rγc） 的共同 γ 链缺失改变了增强人类植入的游戏规则14，15，16，17。替代模型，例如BRG和NRG小鼠，通过删除Rag1或Rag2基因来实现T细胞和B细胞细胞缺乏，这是T细胞受体基因重排所必需的，因此淋巴细胞的成熟和存活18，19。本文使用的BRGS（BALB / c -Rag2 nullIl2RγCnullSirpα NOD）小鼠结合了IL-2Rγ链缺陷和Rag2-/-背景上的NOD SIRPα等位基因，导致没有T，B或NK细胞的高度免疫缺陷小鼠，但具有足够的活力和健康以允许长期植入超过30周13。
HIS小鼠可以通过多种方式产生，人PBMC注射是最直接的方法15，18，20。然而，这些小鼠具有活化的人T细胞的显着扩增，导致移植物抗宿主病（GVHD）在12周龄时，阻止了长期研究。或者，来自脐带血（CB）、骨髓和胎儿肝脏的人造血干细胞也可用于从头植入和生产人体免疫系统。在该系统中，造血干细胞产生多谱系人类免疫系统，与主要发育T细胞的PBMC小鼠相比，T，B和先天免疫细胞的产生对小鼠宿主具有重要的耐受性。因此，GVHD 不存在或大大延迟，研究可以扩展到 10 个月大的小鼠。CB提供了一种简单，可及且无创的CD34 +人造血干细胞来源，有助于植入具有遗传相同免疫系统的多只HIS小鼠17，18，20，21。在过去的几年中，HIS小鼠模型已被广泛用于研究免疫疗法和TME3，4，5，6。尽管这些小鼠发育了人类来源的免疫系统，但与对照免疫缺陷小鼠相比，人类异种移植肿瘤的生长速度相似，并且允许癌细胞和免疫细胞之间的复杂相互作用，这对于维持移植PDX的微环境很重要3，7，8.该协议已被用于进行50多项研究，测试具有PDX和CDX的HIS-BRGS小鼠的治疗。一个重要的结论是，HIS小鼠中的人类肿瘤保持其独特的TME，这是通过相对于初始患者样本和免疫浸润特征的肿瘤的分子评估所定义的3，22，23。我们小组专注于使用多参数流式细胞术深入评估免疫器官和肿瘤中的HIS。在此，我们描述了用于BRGS小鼠人源化，嵌合体评估，人类肿瘤植入，肿瘤生长测量，癌症治疗给药以及通过流式细胞术分析HIS细胞的方案。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>1 mL syringe w/needles</td>
			<td>McKesson</td>
			<td>1031815</td>
			<td></td>
		</tr>
		<tr>
			<td>15 mL tubes</td>
			<td>Grenier Bio-One</td>
			<td>188271</td>
			<td></td>
		</tr>
		<tr>
			<td>2-mercaptoethanol</td>
			<td>Sigma</td>
			<td>M6250</td>
			<td></td>
		</tr>
		<tr>
			<td>50 mL tubes</td>
			<td>Grenier Bio-One</td>
			<td>227261</td>
			<td></td>
		</tr>
		<tr>
			<td>AutoMACS Pro Separator</td>
			<td>Miltenyi</td>
			<td>130-092-545</td>
			<td></td>
		</tr>
		<tr>
			<td>BD Golgi Stop Protein Transport Inhibitor with monensin</td>
			<td>BD Bioscience</td>
			<td>BDB563792</td>
			<td></td>
		</tr>
		<tr>
			<td>BSA</td>
			<td>Fisher Scientific</td>
			<td>BP1600100</td>
			<td></td>
		</tr>
		<tr>
			<td>Cell Stim Cocktail</td>
			<td>Life Technologies</td>
			<td>509305</td>
			<td></td>
		</tr>
		<tr>
			<td>Chill 15 Rack</td>
			<td>Miltenyi</td>
			<td>130-092-952</td>
			<td></td>
		</tr>
		<tr>
			<td>Cotton-plugged glass pipettes</td>
			<td>Fisher Scientific</td>
			<td>13-678-8B</td>
			<td></td>
		</tr>
		<tr>
			<td>Cultrex Basement membrane extract</td>
			<td>R&#38;D Systems</td>
			<td>363200502</td>
			<td></td>
		</tr>
		<tr>
			<td>Cytek Aurora</td>
			<td>Cytek</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>DNase</td>
			<td>Sigma</td>
			<td>9003-98-9</td>
			<td></td>
		</tr>
		<tr>
			<td>eBioscience FoxP3/Transcription Factor Staining Buffer Set</td>
			<td>Invitrogen</td>
			<td>00-5523-00</td>
			<td></td>
		</tr>
		<tr>
			<td>Embryonic Stemcell FCS</td>
			<td>Gibco</td>
			<td>10439001</td>
			<td></td>
		</tr>
		<tr>
			<td>Eppendorf Tubes; 1.5 mL volume</td>
			<td>Grenier Bio-One</td>
			<td>616201</td>
			<td></td>
		</tr>
		<tr>
			<td>Excel</td>
			<td>Microsoft</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>FBS</td>
			<td>Benchmark</td>
			<td>100-106 500mL</td>
			<td></td>
		</tr>
		<tr>
			<td>Ficoll Hypaque</td>
			<td>GE Healthcare</td>
			<td>45001752</td>
			<td></td>
		</tr>
		<tr>
			<td>FlowJo Software</td>
			<td>BD Biosciences</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Forceps - fine</td>
			<td>Roboz Surgical&#160;</td>
			<td>RS5045</td>
			<td></td>
		</tr>
		<tr>
			<td>Forceps normal</td>
			<td>Dumont</td>
			<td>RS4919</td>
			<td></td>
		</tr>
		<tr>
			<td>Formaldehyde</td>
			<td>Fisher</td>
			<td>F75P1GAL</td>
			<td></td>
		</tr>
		<tr>
			<td>Frosted Glass Slides</td>
			<td>Corning</td>
			<td>1255310</td>
			<td></td>
		</tr>
		<tr>
			<td>Gentlemacs C-Tubes</td>
			<td>Miltenyi&#160;&#160;&#160;</td>
			<td>130-096-334</td>
			<td></td>
		</tr>
		<tr>
			<td>GentleMACS Dissociator</td>
			<td>Miltenyi</td>
			<td>130-093-235</td>
			<td></td>
		</tr>
		<tr>
			<td>glass pipettes</td>
			<td>DWK Life Sciences</td>
			<td>63A53</td>
			<td></td>
		</tr>
		<tr>
			<td>Glutamax</td>
			<td>Gibco</td>
			<td>11140050</td>
			<td></td>
		</tr>
		<tr>
			<td>HBSS w/ Ca &#38; Mg</td>
			<td>Sigma</td>
			<td>55037C</td>
			<td></td>
		</tr>
		<tr>
			<td>HEPES</td>
			<td>Corning</td>
			<td>MT25060CI</td>
			<td></td>
		</tr>
		<tr>
			<td>IgG standard</td>
			<td>Sigma</td>
			<td>I2511</td>
			<td></td>
		</tr>
		<tr>
			<td>IgM standard</td>
			<td>Sigma</td>
			<td>401108</td>
			<td></td>
		</tr>
		<tr>
			<td>IMDM</td>
			<td>Gibco</td>
			<td>12440053</td>
			<td></td>
		</tr>
		<tr>
			<td>Liberase DL</td>
			<td>Roche</td>
			<td>5466202001</td>
			<td></td>
		</tr>
		<tr>
			<td>LIVE/DEAD Fixable Blue</td>
			<td>Thermo</td>
			<td>L23105</td>
			<td></td>
		</tr>
		<tr>
			<td>MDA-MB-231</td>
			<td>ATCC</td>
			<td>HTB-26</td>
			<td></td>
		</tr>
		<tr>
			<td>MEM</td>
			<td>Gibco</td>
			<td>1140050</td>
			<td></td>
		</tr>
		<tr>
			<td>mouse anti-human IgG-AP</td>
			<td>Southern Biotech</td>
			<td>JDC-10</td>
			<td></td>
		</tr>
		<tr>
			<td>mouse anti-human IgG-unabeled</td>
			<td>Southern Biotech</td>
			<td>H2</td>
			<td></td>
		</tr>
		<tr>
			<td>mouse anti-human IgM-AP</td>
			<td>Southern Biotech</td>
			<td>UHB</td>
			<td></td>
		</tr>
		<tr>
			<td>mouse anti-human IgM-unlabeled</td>
			<td>Southern Biotech</td>
			<td>SA-DA4</td>
			<td></td>
		</tr>
		<tr>
			<td>MultiRad 350</td>
			<td>Precision X-Ray</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>PBS</td>
			<td>Corning</td>
			<td>45000-446</td>
			<td></td>
		</tr>
		<tr>
			<td>Pen Strep</td>
			<td>Gibco</td>
			<td>15140122</td>
			<td></td>
		</tr>
		<tr>
			<td>Petri Dishes</td>
			<td>Fisher Scientific</td>
			<td>FB0875713A</td>
			<td></td>
		</tr>
		<tr>
			<td>p-nitrophenyl substrate</td>
			<td>Thermo</td>
			<td>34045</td>
			<td></td>
		</tr>
		<tr>
			<td>PRISM</td>
			<td>Graphpad</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Rec Hu FLT3L</td>
			<td>R&#38;D systems</td>
			<td>308-FK-005/CF</td>
			<td></td>
		</tr>
		<tr>
			<td>Rec Hu IL6</td>
			<td>R&#38;D systems</td>
			<td>206-IL-010/CF</td>
			<td></td>
		</tr>
		<tr>
			<td>Rec Hu SCF</td>
			<td>R&#38;D systems</td>
			<td>255SC010</td>
			<td></td>
		</tr>
		<tr>
			<td>RPMI 1640</td>
			<td>Corning</td>
			<td>45000-39</td>
			<td></td>
		</tr>
		<tr>
			<td>Saponin</td>
			<td>Sigma</td>
			<td>8047-15-2</td>
			<td></td>
		</tr>
		<tr>
			<td>Scissors</td>
			<td>McKesson</td>
			<td>862945</td>
			<td></td>
		</tr>
		<tr>
			<td>Serological pipettes 25 mL</td>
			<td>Fisher Scientific</td>
			<td>1367811</td>
			<td></td>
		</tr>
		<tr>
			<td>Sterile filter</td>
			<td>Nalgene</td>
			<td>567-0020</td>
			<td></td>
		</tr>
		<tr>
			<td>Sterile molecular water</td>
			<td>Sigma</td>
			<td>7732-18-5</td>
			<td></td>
		</tr>
		<tr>
			<td>Yeti Cell Analyzer</td>
			<td>Bio-Rad</td>
			<td>12004279</td>
			<td></td>
		</tr>
		<tr>
			<td>Zombie Green</td>
			<td>biolegend</td>
			<td>423112</td>
			<td></td>
		</tr>
	</tbody>
</table>

testing cancer immunotherapeutics in a humanized mouse model bearing human tumors

逆转肿瘤微环境的免疫抑制性质对于用免疫治疗药物成功治疗癌症至关重要。鼠癌模型的多样性极其有限，并且无法转化为临床。为了作为免疫治疗研究的更生理学的临床前模型，已经开发了该协议来评估用人类免疫系统重组的小鼠中人类肿瘤的治疗。这种独特的方案展示了人类免疫系统（HIS，“人源化”）小鼠的发展，然后植入人类肿瘤，细胞系衍生异种移植（CDX）或患者来源的异种移植（PDX）。HIS小鼠是通过将从脐带血中分离的CD34 +人造血干细胞注射到新生儿BRGS（BALB / c Rag2-/- IL2RγC-/- NODSIRPα）高度免疫缺陷的小鼠中产生的，这些小鼠也能够接受异种肿瘤。强调了人体免疫系统发育和肿瘤植入的动力学和特征的重要性。最后，描述了使用流式细胞术对肿瘤微环境的深入评估。在使用该方案的众多研究中，发现单个肿瘤的肿瘤微环境在HIS-PDX小鼠中被概括;“热”肿瘤表现出大的免疫浸润，而“冷”肿瘤则没有。该模型是针对各种人类肿瘤的联合免疫疗法的试验场，也是寻求个性化医疗的重要工具。

按照侧腹肿瘤方案和实验时间表（图1），在两种不同的人结直肠癌（CRC）PDX中研究了肿瘤生长和对靶向酪氨酸激酶抑制剂（TKI）治疗和纳武利尤单抗联合治疗的免疫反应。TKI药物已在免疫缺陷宿主中进行了研究，以评估肿瘤生长仅29。该模型能够单独研究TKI免疫反应的变化，更重要的是，与抗PD-1联合使用。这项研究的重点是两个不同实验中的联合治疗队列...

Watch this Scientific Journal Video about Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors at JoVE.com

Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors

该协议概述了用于免疫肿瘤学研究的人免疫系统（HIS）小鼠的产生。介绍了使用该模型在植入该模型中的人类肿瘤上测试人类免疫疗法的说明和注意事项，重点是表征人类免疫系统对肿瘤的反应。

在携带人类肿瘤的人源化小鼠模型中测试癌症免疫疗法

Reversing the immunosuppressive nature of the tumor microenvironment is critical for the successful treatment of cancers with immunotherapy drugs. Murine ...

该协议概述了用于临床前免疫肿瘤学研究的人类免疫系统或HIS小鼠的产生。小鼠癌症模型的多样性有限，对临床的转化效果很差。该技术通过评估具有人类免疫系统的小鼠中人类肿瘤的治疗，作为免疫治疗研究的临床前模型。人源化小鼠模型可用于研究人类免疫学的多个方面，包括对许多感染或人类免疫系统癌症的反应。获取可靠而强大的脐带血来源并维持免疫缺陷小鼠群体的健康可能具有挑战性。流式细胞术和免疫学分析方面的专业知识至关重要。演示该程序的将是我实验室的研究服务专业人员克里斯蒂娜·拉森（Kristina Larsen）。首先，将从脐带血中分离的CD34阳性细胞沉淀重悬于300微升磁性细胞分离缓冲液中，每1次10次重悬至第八个细胞。向第八个细胞中每1次10加入100微升FCR封闭试剂，然后每1次10次向第八个细胞加入100微升CD34阳性磁珠，并在4摄氏度下孵育30分钟。接下来，向第八个细胞中每10倍加入5毫升磁性细胞分离器缓冲液，并在4摄氏度下以360g旋转10分钟。重复洗涤步骤，并将沉淀重悬于每1亿个磁性细胞分离器缓冲液的500微升中，在标记未分级的15毫升锥形管中。再标记两个 15 毫升管 CD34 阴性和 CD34 阳性 将三个试管放在冷却架上。使用生物安全柜中自动磁性细胞分离器上的两列正向选择程序分离细胞。接下来，为了扩增和冷冻CD34阳性的人干细胞，按照手稿中所述制备脐带血或CB培养基，并通过0.22微米的过滤器。将CD34阳性细胞重悬于每毫升CB培养基100， 000，并在37摄氏度下孵育。在第三天，向烧瓶中加入等体积的不含细胞因子的CB培养基。在第五天，收获扩增的CD34阳性细胞。上下移液细胞悬液，并收集在50毫升锥形管中。加入足够的CB培养基以覆盖烧瓶底部。使用细胞刮刀刮擦烧瓶的整个底部。将所有培养基收集到同一个50毫升管中，然后离心。将细胞重悬于两毫升CB培养基中，然后离心。将培养基向下吸出到沉淀中，然后将沉淀重新悬浮在冷冻介质中。接下来，在幼崽照射后三小时开始CD34阳性细胞制备。在50毫升的管中加热10毫升CB培养基。每四到六只幼崽注射一瓶体外扩增和冷冻的CD34阳性细胞。在50至55摄氏度下快速解冻，直到只看到少量冰，然后将细胞添加到加热的CB培养基中。使用一毫升培养基冲洗每个小瓶，并在4摄氏度下以360g旋转细胞12分钟。小心吸出培养基。将沉淀重悬于两毫升CB培养基中并计数细胞。再次，离心细胞，吸出培养基，并将沉淀重悬于每n加一个幼崽的100微升无菌PBS中，导致每只小鼠250， 000至450， 000个CD34阳性细胞。对于从小鼠血液中分离的PBMC，通过轻轻上下移液混合血液肝素，并缓慢覆盖在500微升1.077克/毫升密度梯度的顶部，注意不要干扰界面。在室温下以1， 220 g离心管20分钟，无间断。用 200 微升移液管从血沉棕黄层中取出尽可能多的细胞，并添加到含有 750 微升收获培养基的新 1.5 毫升管中。以360克离心11分钟。将培养基吸出至50微升，并将沉淀重悬于750微升收获培养基中。在流式细胞仪上获取每个样品100微升的数据。然后将 fcs 文件导入流数据编辑软件，并将多边形门应用于 FSC-A 与 SSC-A 图。将轴更改为 FSC-A 而不是 FSC-H，并在线性对角线上对单元格进行门控，不包括从线上突出的双峰。选择这些细胞并将轴更改为 hCD45 而不是 mCD45。将多边形门应用于 hCD45 阳性群体，并应用名称 human。将多边形门应用于 mCD45 阳性群体，并应用名称鼠标。为人类和小鼠种群创建计数统计量。接下来，选择人群，并将轴更改为CD19与CD3。将多边形门应用于CD19阳性细胞，并将其命名为B细胞。对CD3阳性群体应用多边形门，并将其命名为T细胞。然后将多边形门应用于双重阴性总体，并将其命名为 non-TB。选择 T 细胞群并将轴更改为 CD4 与 CD3。将多边形门应用于 CD4 阳性群体，并将其命名为 CD4 阳性。将多边形门应用于 CD4 阴性群体，并将其命名为 CD8。选择非结核病人群，并将轴更改为 CD56 与骨髓。将多边形门应用于总CD56阳性群体，并将其命名为NK细胞。然后将多边形门应用于CD56阴性和髓系阳性群体，并将其命名为骨髓。为所有总体的百分比和计数统计数据创建一个表，并将其导出到电子表格。使用指示的公式计算hCD45嵌合体的百分比。在小鼠中生长肿瘤细胞并给予药物治疗后，收获组织。将鼠标放在带有销钉的泡沫解剖板上以将其固定到位，并将手臂和腿伸展 45 度。从骨盆附近开始，在躯干中间切开一个切口，一直延伸到下巴。将皮肤拉到边缘，并用别针将其固定到位。使用细镊子按腋窝、宫颈、肠系膜、腹股沟和食管裂孔顺序拔除淋巴结。将淋巴结放在磨砂玻璃载玻片的一侧，在八毫升收获培养基中的培养皿中。以垂直角度握住载玻片，磨砂边缘向内，轻轻按压组织，直到释放细胞内容物。通过将载玻片拉开并一起冲洗载玻片几次，以释放最大数量的细胞。用 5 英寸玻璃移液管收集细胞，并通过 9 英寸棉塞移液管将它们过滤到标记的 15 毫升锥形管中。接下来，用镊子握住肿瘤，同时用解剖剪刀缓慢剪断肿瘤边缘，从开放的侧翼提取肿瘤。称量肿瘤并去除 1/4 的肿瘤以进行 RNA 和免疫组织化学处理。将剩余的 3/4 肿瘤放入 6 厘米的培养皿中，并使用手术刀刀片将其切成 1 毫米的碎片。将肿瘤碎片转移到解离管中。然后用不完整的TIL培养基冲洗培养皿，并将其添加到管中。加入胶原酶制剂，并在37摄氏度下使用机械解离组织30分钟至1小时。将悬浮液通过 100 微米过滤器进入 50 毫升锥形管中，并用 10 毫升 TIL 完全培养基冲洗过滤器。将沉淀离心并重悬于含有DNase的足够收获培养基中，以便细胞悬液可以轻松通过P1000移液器吸头并记录体积以进行下游分析。在PDX CRC 307P中，联合治疗减缓了肿瘤的生长，这取决于肿瘤随时间的生长体积，肿瘤重量和特定生长速率。在不同小鼠队列中测试的PDX CRC 307M受HIS BRGS小鼠相同组合治疗的影响较小。基于肿瘤植入前血液中人hCD45阳性和人T细胞hCD3阳性嵌合体的总体情况，与治疗的CRC 307P携带小鼠联合使用外周免疫系统和TIL中的两个参数都增加了，但CRC 307M模型没有。对人类T细胞的研究显示，CRC 307P肿瘤中有更多的活化T细胞，但联合治疗小鼠的淋巴液没有。此外，在联合治疗的CRC 307P肿瘤中，有更多的效应记忆CD8阳性T细胞和更少的TIM-3阳性T细胞。相比之下，CRC 307M型号没有注意到这种差异。此外，在联合治疗的小鼠中没有观察到细胞毒性T细胞群频率的变化，尽管在未治疗的小鼠中观察到更高的细胞毒性T细胞。联合治疗不影响CRC 307P淋巴器官或肿瘤中Tregs的频率，尽管CRC 307M数据显示Tregs有减少的趋势。使用流式细胞术提高肿瘤细胞的免疫相关变化。在从组合处理的HIS BRGS小鼠切除的CRC 307P肿瘤细胞上观察到MHC I类和II类的表达增加。在CRC 307M模型中，相同的药物治疗诱导肿瘤细胞上的HLA II类表达。同样，联合治疗导致EpCAM阳性CRC 307P肿瘤细胞上的PD-L1表达增加。最后，研究了免疫应答与肿瘤生长的相关性。增加的CD4阳性T细胞显示出与较小的肿瘤生长显着相关，更具体地说，联合治疗HIS小鼠的HLA-DR阳性活化T细胞。无菌技术同时分离CD34阳性细胞，因为小鼠免疫缺陷极强。由此产生的嵌合在脐带血供体内部和之间是可变的，T细胞具有最大的变异。可以进行无限的免疫治疗组合，以及机制和药物给药动力学研究，例如，删除CD8 T细胞以确认其作用。重要的是，还可以研究与药物相关的毒性。它提供了一个更相关和更易于访问的临床前模型来测试人类免疫疗法以转化为临床。基于这些数据，目前正在进行几项临床试验。

Research

JoVE Journal

Cancer Research

Fluorescent Orthotopic Mouse Model of Pancreatic Cancer

胰腺癌的荧光原位小鼠模型

Pancreatic cancer remains one of the cancers for which survival has not improved substantially in the last few decades. Only 7% of diagnosed patients will ...

科研

癌症研究

In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis

In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis

体内模型对缺氧对肿瘤转移的影响测试

Hypoxia has been implicated in the metastasis of Ewing sarcoma (ES) by clinical observations and in vitro data, yet direct evidence for its pro-metastatic ...

The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia

结肠-26癌荷瘤小鼠为癌症恶病质的研究模型

Cancer cachexia is the progressive loss of skeletal muscle mass and adipose tissue, negative nitrogen balance, anorexia, fatigue, inflammation, and ...

Tumor Engraftment in a Xenograft Mouse Model of Human Mantle Cell Lymphoma

人地幔细胞淋巴瘤移植小鼠模型中肿瘤植入的研究

B lymphocytes are key players in immune cell circulation and they mainly home to and reside in lymphoid organs. While normal B cells only proliferate when ...

Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines

乳腺癌细胞系外周血单核细胞破的人前临床模型的建立

The crosstalk between tumor cells and bone cells in the bone microenvironment is crucial to understanding the mechanism of bone metastasis formation. We ...

A Human Peripheral Blood Mononuclear Cell (PBMC) Engrafted Humanized Xenograft Model for Translational Immuno-oncology (I-O) Research

A Human Peripheral Blood Mononuclear Cell PBMC Engrafted Humanized Xenograft Model for Translational Immuno-oncology I-O Research

用于转化免疫肿瘤学(I-O)研究的人类外周血单核细胞(PBMC)的人工化异种移植模型

The discovery and development of immuno-oncology (I-O) therapy in recent years represents a milestone in the treatment of cancer. However, treatment ...

Murine Model of Metastatic Liver Tumors in the Setting of Ischemia Reperfusion Injury

缺血再灌注损伤中转移性肝肿瘤的模样

Liver ischemia and reperfusion (I/R) injury, a common clinical challenge, remains an inevitable pathophysiological process that has been shown to induce ...

Obtaining Cancer Stem Cell Spheres from Gynecological and Breast Cancer Tumors

从妇科和乳腺癌肿瘤获得癌症干细胞球

Cancer stem cells (CSC) are a small population with self-renewal and plasticity which are responsible for tumorigenesis, resistance to treatment and ...

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells

快速筛选工作流程，利用患者衍生胶质瘤干细胞确定GBM的潜在组合疗法

The glioma stem cells (GSCs) are a small fraction of cancer cells which play essential roles in tumor initiation, angiogenesis, and drug resistance in ...

High-Resolution Ultrasonography for the Analysis of Orthotopic ATC Tumors in a Genetically Engineered Mouse Model

用于分析基因工程小鼠模型中原位ATC肿瘤的高分辨率超声检查

Anaplastic thyroid carcinoma (ATC) is associated with a poor prognosis and short median survival time, but no effective treatment improves the outcomes ...