Name: stereotactic adoptive transfer of cytotoxic immune cells in murine models of orthotopic human glioblastoma multiforme xenografts
Uploaded: 2018-09-01T13:00:00
Description: Watch this Scientific Journal Video about Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts at JoVE.com

作者感谢南特大学医院动物设施 (犹特人) 的工作人员畜牧和护理, 南特大学的细胞和 tissular 成像核心设施 (MicroPICell) 的成像, 和从南特的细胞术设施 (Cytocell)他们的专家技术援助。这项工作由 INSERM、CNRS、大学 de 南特、国立杜肿瘤研究所 (INCa#PLBio2014-155)、国家民族反癌症 (AO 区域间 2017) 和欧洲联盟时代网 Transcan2 (Immunoglio) 资助。这支队伍由研究所 Medicale (DEQ20170839118) 资助。这项工作是在 LabEX 监察员办公室和 IHU Cesti 方案的范围内实现的, 该项目分别由艾文莉和 ANR-11-LABX-0016-01 的国家研究机构 Investissements d ' ANR-10-IBHU-005 支助。IHU-Cesti 项目也支持南特都市和支付 la 卢瓦尔地区。作者感谢 Chirine Rafia 为改正手稿提供帮助。

下列涉及动物的程序是根据机构指南 (协议 #00186) 执行的. 02; 意大利 (法国) 的区域道德委员会人类 PBMCs 从知情的健康捐献者的血液中分离出来 (景区法国法国南特)。所有步骤都是在无菌条件下进行的。
1. 细胞毒性效应 T 淋巴细胞的非特异扩张
<ol><li>准备并照射35的馈线细胞。为刺激 2 x 105 -4 x 105个效应细胞, 准备 10 x 106 PBMCs 和 1 x 106 BLCLs 从?...

<ol>
	<li>Stupp, R., Roila, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Malignant+glioma:+ESMO+clinical+recommendations+for+diagnosis,+treatment+and+follow-up.">Malignant glioma: ESMO clinical recommendations for diagnosis, treatment and follow-up.</a> Annals of Oncology. 20 Suppl 4, 126-128 (2009).</li><li>Weller, M., Cloughesy, T., Perry, J. R., Wick, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Standards+of+care+for+treatment+of+recurrent+glioblastoma--are+we+there+yet?.">Standards of care for treatment of recurrent glioblastoma--are we there yet?.</a> Neuro-Oncology. 15 (1), 4-27 (2013).</li><li>Chen, S. H., Shine, H. D., Goodman, J. C., Grossman, R. G., Woo, S. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gene+therapy+for+brain+tumors:+regression+of+experimental+gliomas+by+adenovirus-mediated+gene+transfer+in+vivo.">Gene therapy for brain tumors: regression of experimental gliomas by adenovirus-mediated gene transfer in vivo.</a> Proceedings of the National Academy of Sciences of the United States of America. 91 (8), 3054-3057 (1994).</li><li>Choi, P. J., Tubbs, R. S., Oskouian, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Emerging+Cellular+Therapies+for+Glioblastoma+Multiforme.">Emerging Cellular Therapies for Glioblastoma Multiforme.</a> Cureus. 10 (3), e2305 (2018).</li><li>Zhu, L., 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=Targeting+and+Therapy+of+Glioblastoma+in+a+Mouse+Model+Using+Exosomes+Derived+From+Natural+Killer+Cells.">Targeting and Therapy of Glioblastoma in a Mouse Model Using Exosomes Derived From Natural Killer Cells.</a> Frontiers in Immunology. 9, 824 (2018).</li><li>Chung, D. S., Shin, H. J., Hong, Y. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+hope+in+immunotherapy+for+malignant+gliomas:+adoptive+T+cell+transfer+therapy.">A new hope in immunotherapy for malignant gliomas: adoptive T cell transfer therapy.</a> Journal of Immunology Research. 2014, 326545 (2014).</li><li>Vauleon, E., Avril, T., Collet, B., Mosser, J., Quillien, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Overview+of+cellular+immunotherapy+for+patients+with+glioblastoma.">Overview of cellular immunotherapy for patients with glioblastoma.</a> Clinical and Developmental Immunology. 2010, (2010).</li><li>Brown, C. 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=Regression+of+Glioblastoma+after+Chimeric+Antigen+Receptor+T-Cell+Therapy.">Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy.</a> The New England of Journal of Medicine. 375 (26), 2561-2569 (2016).</li><li>Jarry, U., 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=Stereotaxic+administrations+of+allogeneic+human+Vgamma9Vdelta2+T+cells+efficiently+control+the+development+of+human+glioblastoma+brain+tumors.">Stereotaxic administrations of allogeneic human Vgamma9Vdelta2 T cells efficiently control the development of human glioblastoma brain tumors.</a> Oncoimmunology. 5 (6), e1168554 (2016).</li><li>Dutoit, V., 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=Exploiting+the+glioblastoma+peptidome+to+discover+novel+tumour-associated+antigens+for+immunotherapy.">Exploiting the glioblastoma peptidome to discover novel tumour-associated antigens for immunotherapy.</a> Brain. 135 (Pt 4), 1042-1054 (2012).</li><li>Joalland, 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=IL-21+Increases+the+Reactivity+of+Allogeneic+Human+Vgamma9Vdelta2+T+Cells+Against+Primary+Glioblastoma+Tumors.">IL-21 Increases the Reactivity of Allogeneic Human Vgamma9Vdelta2 T Cells Against Primary Glioblastoma Tumors.</a> Journal of Immunotherapy. 41 (5), 224-231 (2018).</li><li>Clemenceau, B., 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=Effector+memory+alphabeta+T+lymphocytes+can+express+FcgammaRIIIa+and+mediate+antibody-dependent+cellular+cytotoxicity.">Effector memory alphabeta T lymphocytes can express FcgammaRIIIa and mediate antibody-dependent cellular cytotoxicity.</a> The Journal of Immunology. 180 (8), 5327-5334 (2008).</li><li>Abdelwahab, M. G., Sankar, T., Preul, M. C., Scheck, A. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intracranial+implantation+with+subsequent+3D+in+vivo+bioluminescent+imaging+of+murine+gliomas.">Intracranial implantation with subsequent 3D in vivo bioluminescent imaging of murine gliomas.</a> Journal of Visualized Experiments. (57), e3403 (2011).</li><li>Jarry, U., 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=Treg+depletion+followed+by+intracerebral+CpG-ODN+injection+induce+brain+tumor+rejection.">Treg depletion followed by intracerebral CpG-ODN injection induce brain tumor rejection.</a> Journal of Neuroimmunology. 267 (1-2), 35-42 (2014).</li><li>June, C. H., O'Connor, R. S., Kawalekar, O. U., Ghassemi, S., Milone, M. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=CAR+T+cell+immunotherapy+for+human+cancer.">CAR T cell immunotherapy for human cancer.</a> Science. 359 (6382), 1361-1365 (2018).</li><li>Baruch, E. N., Berg, A. L., Besser, M. J., Schachter, J., Markel, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adoptive+T+cell+therapy:+An+overview+of+obstacles+and+opportunities.">Adoptive T cell therapy: An overview of obstacles and opportunities.</a> Cancer. 123 (S11), 2154-2162 (2017).</li><li>Bryant, N. L., 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+and+immunotherapeutic+potential+of+gammadelta+T-cells+in+patients+with+glioblastoma.">Characterization and immunotherapeutic potential of gammadelta T-cells in patients with glioblastoma.</a> Neuro-Oncology. 11 (4), 357-367 (2009).</li><li>Pereboeva, L., Harkins, L., Wong, S., Lamb, L. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+safety+of+allogeneic+innate+lymphocyte+therapy+for+glioma+patients+with+prior+cranial+irradiation.">The safety of allogeneic innate lymphocyte therapy for glioma patients with prior cranial irradiation.</a> Cancer Immunology, Immunotherapy. 64 (5), 551-562 (2015).</li><li>Bailey, S. L., Carpentier, P. A., McMahon, E. J., Begolka, W. S., Miller, S. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Innate+and+adaptive+immune+responses+of+the+central+nervous+system.">Innate and adaptive immune responses of the central nervous system.</a> Critical Reviews in Immunology. 26 (2), 149-188 (2006).</li><li>Louveau, 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=Structural+and+functional+features+of+central+nervous+system+lymphatic+vessels.">Structural and functional features of central nervous system lymphatic vessels.</a> Nature. 523 (7560), 337-341 (2015).</li><li>Menei, 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=Local+and+sustained+delivery+of+5-fluorouracil+from+biodegradable+microspheres+for+the+radiosensitization+of+glioblastoma:+a+pilot+study.">Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of glioblastoma: a pilot study.</a> Cancer. 86 (2), 325-330 (1999).</li><li>Menei, 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=Stereotaxic+implantation+of+5-fluorouracil-releasing+microspheres+in+malignant+glioma.">Stereotaxic implantation of 5-fluorouracil-releasing microspheres in malignant glioma.</a> Cancer. 100 (2), 405-410 (2004).</li><li>Salot, 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=Large+scale+expansion+of+gamma+9+delta+2+T+lymphocytes:+Innacell+gamma+delta+cell+therapy+product.">Large scale expansion of gamma 9 delta 2 T lymphocytes: Innacell gamma delta cell therapy product.</a> Journal of Immunological Methods. 326 (1-2), 63-75 (2007).</li><li>Bennouna, 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=Phase-I+study+of+Innacell+gammadelta,+an+autologous+cell-therapy+product+highly+enriched+in+gamma9delta2+T+lymphocytes,+in+combination+with+IL-2,+in+patients+with+metastatic+renal+cell+carcinoma.">Phase-I study of Innacell gammadelta, an autologous cell-therapy product highly enriched in gamma9delta2 T lymphocytes, in combination with IL-2, in patients with metastatic renal cell carcinoma.</a> Cancer Immunology, Immunotherapy. 57 (11), 1599-1609 (2008).</li><li>Singh, S. K., 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=Identification+of+human+brain+tumour+initiating+cells.">Identification of human brain tumour initiating cells.</a> Nature. 432 (7015), 396-401 (2004).</li></ol>

经选择的本机或工程免疫效应细胞的移植, 是有效治疗肿瘤的一种有希望的方法, 如浸润性脑癌, 注意限制活性对非转化细胞15, 16,17,18。然而, 包括大脑在内的中枢神经系统具有特殊的免疫状态, 特别是由于血脑屏障的存在以及缺乏典型的淋巴引流系统19、20。...

肾小球 (IV. 型星形细胞瘤) 是成人最常见和最有攻击性的原发性脑癌。尽管有积极的治疗, 结合手术和射频化疗, 肾小球仍然与一个非常糟糕的预后 (中位存活率14.6 月和2年死亡率 > 73%)1。这一证据表明, 在过去十年2中, 没有有效的治疗进展得到证实。在设计更有效的治疗策略3,4,5, 免疫疗法6的候选者中, 目前正在探索追踪和消除高度侵入性和无线电/抗化疗肿瘤细胞, 怀疑他们的关键贡献迅速和致命的肿瘤复发7。对免疫疗法的各种潜在免疫指标进行了鉴定和建议, 涉及天然或改良的αβ或υδ T 淋巴细胞, 如肾小球特异肿瘤抗原或应力诱导分子8,9, 10。管理选定的肾小球活性免疫细胞效应器的可能性代表了一个独特的机会, 提供高数量的效应淋巴细胞直接进入残余恶性肿瘤的部位。为支持这一策略, 我们最近发现, 基于 immunodeficient 小鼠的同种异体肾小球移植的模型忠实地重述了肾小球肿瘤的发展9,11。此外, 这些模型被用来证明过继转输转移异体人 vυ9vδ2t 淋巴细胞的强抗癌功效。
本协议描述了在同种异体 T 淋巴细胞的移植基础上实现脑肿瘤立体定向免疫疗法的关键实验步骤。本文说明: (i) 治疗同种异体免疫效应 T 淋巴细胞 (如人 vυ9vδ2t 淋巴细胞) 的扩增;(ii) 制备注射用的这些效应 T 淋巴细胞;(iii) 大脑内立体定向管理的程序, 靠近肿瘤。本文还介绍了立体定向注射后这些细胞效应的行为。
这里提出的治疗方法是基于每剂量 20 x 106效应细胞为每个脑肿瘤-轴承 immunodeficient 鼠注射。一个初始的体外扩张步骤是需要产生大量的免疫细胞。因此, 非特异细胞扩张是使用 phytohemagglutinin (PHA L) 和辐照异基因饲养细胞: 外周血单个核细胞 (PBMCs) 的健康捐献者和 eb 病毒 (eb) 转换的 B-永生细胞线 (BLCLs), 从 PBMCs 的体外感染, 从狨 B95-8 细胞系的 eb 病毒的培养上清液中提取, 在1µg/毫升环孢素 a 的存在。
从体外测定9中比较和选择了肾小球活性效应免疫细胞。这些效应细胞的激活和放大使用标准协议, 根据其性质 (例如, 人类 Vγ9Vδ2 T 淋巴细胞9或人抗疱疹病毒αβ T 淋巴细胞12) 与最低纯度 > 80%, 例行由细胞分析检查。下面详述的细胞扩张程序适用于各种人类淋巴细胞子集。

<table border="0" cellpadding="0" cellspacing="0" style="width:825px;" width="825">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">PBMCs</td>
			<td style="width:136px;"></td>
			<td style="width:119px;"></td>
			<td style="width:232px;">from 3 different healthy donors</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">BLCLs</td>
			<td style="width:136px;"></td>
			<td style="width:119px;"></td>
			<td>from 3 different donors</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:339px;">Roswell Park Memorial Institute medium (RPMI)</td>
			<td style="width:136px;">Gibco</td>
			<td>31870-025</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:339px;">FCS</td>
			<td style="width:136px;">Dutscher</td>
			<td style="width:119px;">S1810-500</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">L-glutamine</td>
			<td style="width:136px;">Gibco</td>
			<td style="width:119px;">25030-024</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">penicillin/streptomycin</td>
			<td style="width:136px;">Gibco</td>
			<td style="width:119px;">15140-122</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">IL-2</td>
			<td style="width:136px;">Novartis</td>
			<td style="width:119px;">proleukin</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">PHA-L</td>
			<td style="width:136px;">Sigma</td>
			<td>L4144</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">Stereotaxic frame</td>
			<td>Stoelting Co.</td>
			<td align="right">51600</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">Mouse adaptator for stereotaxic frame&#160;&#160;</td>
			<td>Stoelting Co.</td>
			<td align="right">51624</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">microsyringe pump injector&#160;</td>
			<td style="width:136px;">WPI</td>
			<td style="width:119px;">UMP3-4</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">NanoFil Syringe</td>
			<td style="width:136px;">WPI</td>
			<td style="width:119px;">NF34BV-2</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">NSG mice</td>
			<td style="width:136px;">Charles River</td>
			<td style="width:119px;">NSGSSFE07S</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">Ketamine</td>
			<td style="width:136px;">Merial</td>
			<td style="width:119px;">Imalg&#232;ne 1000</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">Xylazine</td>
			<td style="width:136px;">Bayer</td>
			<td style="width:119px;">Rompur 2%</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">Scissors</td>
			<td style="width:136px;">WPI</td>
			<td style="width:119px;">201758</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">Forceps</td>
			<td style="width:136px;">WPI</td>
			<td style="width:119px;">501215</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">OmniDrill 115/230V</td>
			<td style="width:136px;">WPI</td>
			<td align="right">503598</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">Vicryl 4-0</td>
			<td style="width:136px;">Ethicon</td>
			<td>VCP397H</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:339px;">Xylocaine</td>
			<td style="width:136px;">Astrazeneca</td>
			<td>3634461</td>
			<td></td>
		</tr>
	</tbody>
</table>

stereotactic adoptive transfer of cytotoxic immune cells in murine models of orthotopic human glioblastoma multiforme xenografts

胶质瘤多形性 (肾小球) 是成人中最常见和最有攻击性的原发性脑癌, 通常与预后较差有关, 在过去十年中提出了缺乏有效的治疗方法。在设计新的治疗策略的有希望的候选者中, 细胞免疫疗法已被用来消除高度侵袭性和化疗放射抗拒肿瘤细胞, 可能涉及迅速和致命复发的癌症。因此, 在肿瘤附近的同种异体肾小球-反应性免疫细胞效应剂 (如人 vυ9vδ2 T 淋巴细胞) 的管理, 将是一个独特的机会, 以提供高效和高度集中的治疗药物直接进入脑恶性肿瘤现场。在这里, 我们提出了一项协议, 以制备和立体定向管理的异基因人淋巴细胞在 immunodeficient 小鼠携带原位人原发性脑肿瘤。本研究为这些细胞免疫疗法的可行性和抗肿瘤效果提供了一个临床前的概念证明, 它们依赖于 intrabrain 肿瘤床内的异基因人淋巴细胞的立体定向注射。

这项研究描述了在肿瘤携带的小鼠脑内进行细胞免疫效应细胞转移的策略, 其基础是直接在瘤床内进行的立体定向注射。
为了尽量减少与大注射量相关的脑损伤的风险, 需要将效应细胞悬浮液集中 (20 x 106细胞在 PBS 的 15-20 µL 中)。为了检查这个细胞浓度步骤是否可能影响效应细胞的生存能力, 这些细胞是根据所描述的协...

Watch this Scientific Journal Video about Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts at JoVE.com

Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts

立体定向移植人胶质瘤多形性移植小鼠细胞毒性免疫细胞模型的研究

在这里, 我们提出了一项协议, 以制备和立体定向管理的异基因人淋巴细胞在 immunodeficient 小鼠携带原位人原发性脑肿瘤。本研究为 intrabrain 细胞免疫疗法的可行性和抗肿瘤疗效提供了概念验证。

Glioblastoma multiforme (GBM), the most frequent and aggressive primary brain cancer in adults, is generally associated with a poor prognosis, and scarce ...

Research

JoVE Journal

Immunology and Infection

Experimental Metastasis and CTL Adoptive Transfer Immunotherapy Mouse Model

实验转移和CTL过继转移免疫小鼠模型

Experimental metastasis mouse model is a simple and yet physiologically relevant metastasis model. The tumor cells are injected intravenously (i.v) into ...

科研

免疫与感染

Seven Steps to Stellate Cells

星状细胞的七个步骤

Hepatic stellate cells are liver-resident  cells of star-like morphology and are located in the space of Disse between  liver sinusoidal endothelial cells ...

Flow Cytometry Analysis of Immune Cells Within Murine Aortas

流式细胞仪分析小鼠主动脉内流的免疫细胞

Atherosclerosis is a chronic inflammatory process of medium and large size vessels that is characterized by the formation of plaques consisting of foam ...

Overcoming Unresponsiveness in Experimental Autoimmune Encephalomyelitis (EAE) Resistant Mouse Strains by Adoptive Transfer and Antigenic Challenge

Overcoming Unresponsiveness in Experimental Autoimmune Encephalomyelitis EAE Resistant Mouse Strains by Adoptive Transfer and Antigenic Challenge

在实验性自身免疫性脑脊髓炎（EAE）抗性品系小鼠继转移和抗原挑战克服反应迟钝

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) and has been used as an animal model for ...

Accelerated Type 1 Diabetes Induction in Mice by Adoptive Transfer of Diabetogenic CD4+ T Cells

加速1型糖尿病感应在小鼠体内的过继转移致糖尿病的CD4 + T细胞

The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes after 12 weeks of age and is the most extensively studied animal model of ...

Assessing the Development of Murine Plasmacytoid Dendritic Cells in Peyer's Patches Using Adoptive Transfer of Hematopoietic Progenitors

评估小鼠浆细胞树突状细胞在淋巴集结的开发利用造血祖细胞的过继转移

This protocol details a method to analyze the ability of purified hematopoietic progenitors to generate plasmacytoid dendritic cells (pDC) in intestinal ...

Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care

CAR性T细胞过继治疗的护理标准胶质母细胞瘤的上下文生成

Adoptive T cell immunotherapy offers a promising strategy for specifically targeting and eliminating malignant gliomas. T cells can be engineered ex vivo ...

Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice

Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice

诱导小鼠肠道炎症由效应CD4的过继转移<sup&gt; +</sup&gt; CD45RB<sup&gt;高</sup&gt; T细胞免疫缺陷小鼠

There are many different animal models available for studying the pathogenesis of human inflammatory bowel diseases (IBD), each with its own advantages ...