PIDD represent an expanding group of genetic disorders that compromise immunity against bacteria, viruses, and fungi. The most severe forms of PIDD cause profound susceptibility to opportunistic infections due to impaired or absent T-cell immunity. These diseases can be rapidly fatal unless treated via hematopoietic stem cell transplantation (HSCT). Chronic viral illnesses are a common presenting feature of many of these disorders, and studies have shown that survival of HSCT is profoundly impacted by the patient's pre-transplant disease status. Primary infections with viruses such as cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are common, and respiratory viruses such as adenovirus also frequently cause infection. In patients with severe combined immunodeficiency (SCID), a prior study identified these viruses as the most common causes of mortality in the immediate period following HSCT. Though some forms of PIDD are amenable to HSCT without requiring conditioning chemotherapy, many forms require a variable degree of pre-conditioning to ensure that stable engraftment of the donor cells is achieved. The administration of cytotoxic chemotherapy used in the conditioning regimens can however increase the risk for regimen related toxicity and for some patients (especially those with active viral infections) this risk is particularly high, leading to high treatment related mortality rates. For these reasons, many such patients are not even considered candidates for HSCT or are delayed getting to HSCT and ultimately succumb to infection before they can receive the transplant.
The primary objective of this study is to determine the safety of administering third-party multivirus-specific cytotoxic T lymphocytes (mCTL) from adult CMV seropositive donors to treat refractory viral infections in patients with primary immunodeficiency disorders (PIDD) prior to hematopoietic stem cell transplantation (HSCT).

开始日期2014-04-01

申办/合作机构

Children's National Research Institute

NCT01945814

/ Active, not recruiting临床1期IIT

Allogeneic Multivirus - Directed Cytotoxic T Lymphocytes (CTL) Targeting CMV (IE1 and pp65), EBV (LMP2, EBNA1), and Adv (Hexon and Penton)

In this study, investigators are trying to see if infusion of T cells (called CTLs) will prevent or treat cytomegalovirus (CMV), Epstein Barr Virus (EBV) and adenovirus (AdV) reactivation or infection.
Patients with blood cell cancer, other blood disease or a genetic disease may receive a stem cell transplant. After receiving transplant, they are at risk of infections until a new immune system to fight infections grows from the cord blood cells. In this study, investigators are trying to give special cells called T cells. These cells will try to fight viruses that can cause infection.
Investigators will test to see if blood cells from donor that have been grown in a special way, can prevent patients from getting an infection. EBV, AdV and CMV are viruses that can cause serious life-threatening infections in patients who have weak immune systems after transplant.
T lymphocytes can kill viral cells but normally there are not enough of them to kill all the virus infected cells after transplant. Some researcher have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person during a viral infection after a bone marrow transplant. Some of these studies have shown a positive therapeutic effect in patients receiving the CTLs after a viral infection in the post-transplant period.
Investigators will grow these cells from donor in the laboratory in a way that will train them to recognize and remove viruses when the T cells are given after a transplant. Since most donors have previously been infected with EBV, CMV, and adenovirus, investigators are able to use their T cells that remember these viruses to grow the CTLs. However, they now also have a new way of growing CTLs from donors who have not been infected with CMV.

开始日期2014-02-01

申办/合作机构

Children's National Research Institute

100 项与 Multivirus-specific cytotoxic T lymphocytes (mCTLs)(Children's National Research Institute) 相关的临床结果

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100 项与 Multivirus-specific cytotoxic T lymphocytes (mCTLs)(Children's National Research Institute) 相关的转化医学

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100 项与 Multivirus-specific cytotoxic T lymphocytes (mCTLs)(Children's National Research Institute) 相关的专利（医药）

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项与 Multivirus-specific cytotoxic T lymphocytes (mCTLs)(Children's National Research Institute) 相关的文献（医药）

1988-11-01·Journal of immunology (Baltimore, Md. : 1950)

Coxsackievirus B-3-induced myocarditis. Virus and actinomycin D treatment of myocytes induces novel antigens recognized by cytolytic T lymphocytes.

Article

作者: Huber, S A ; Tracy, R ; Heintz, N

BALB/c mice inoculated with 6 x 10(4) plaque-forming units of a myocarditic variant of Coxsackievirus, group B, type 3 (CVB3M) developed three distinct CTL populations recognizing putative virion (virus specific CTL, VCTL), normally expressed heart (autoreactive CTL, ACTL), and aberrant metabolic (MCTL) Ag. Induction of the MCTL-specific Ag on cardiocytes correlated with the ability of the myocarditic viruses and actinomycin D to interfere with cellular metabolism as measured by 3H-uridine and 3H-leucine incorporation. ACTL specifically lysed uninfected cardiocyte targets, but ACTL Ag expression was lost soon after infection of monocytes only to reappear 6 h later. MCTL and VCTL could be separated by adsorption to myocytes treated with either actinomycin D- or UV-inactivated CVB3M. MCTL cross-reactively lysed myocytes infected with another virus suppressing 3H-uridine incorporation (encephalomyocarditis virus) but failed to react to targets infected with viruses not inhibiting cell metabolism. VCTL specifically lysed only cells infected with the homologous virus. ACTL belonged to the CD8 (Lyt-2+) T cell subset, whereas both VCTL and MCTL were CD4 (L3T4+) T cells.

Frontiers in veterinary science2区 · 农林科学

Combined Maternal and Post-Hatch Dietary Supplementation of 25-Hydroxycholecalciferol Alters Early Post-Hatch Broiler Chicken Duodenal Macrophage and Crypt Cell Populations and Their Mitotic Activity

2区 · 农林科学

ArticleOA

作者: Starkey, Charles W ; Avila, Luis P ; Leiva, Samuel F ; Sweeney, Kelly M ; Abascal-Ponciano, Gerardo A ; Wilson, Jeanna L ; Flees, Joshua J ; Starkey, Jessica D

The previous work has demonstrated that maternal supplementation of the circulating metabolite of vitamin D3 (D3), 25-hydroxycholecalciferol (25OHD3), enhances the immunocompetence of broiler chick offspring. In post-hatch broiler diets, 25OHD3 has been shown to affect intestinal morphology and improve the immune status of broilers. An experiment with a 2 × 2 factorial treatment arrangement was conducted to assess the effects of combining maternal (MDIET) and post-hatch (PDIET) dietary 25OHD3 inclusion on duodenal crypt and macrophage cell populations and mitotic activity in young broiler chickens. All diets were formulated to provide 5,000 IU of vitamin D. Broiler breeder hens were offered 1 of 2 MDIET: 5,000 IU D3 per kg of feed (MCTL) or 2,240 IU of D3 + 2,760 IU of 25OHD3 per kg of feed (M25OHD3) from week 25 to 41. Male broiler offspring (n = 480) hatched from eggs collected during week 41 of breeding age were allotted in raised floor pens (4 birds per pen from day 0 to 7 and individually allotted from day 8 to 21). Chicks were fed 1 of 2 PDIET (starter day 0 to 21): 5,000 IU D3 per kg of feed (PCTL) or 2,240 IU D3 + 2,760 IU 25OHD3 (P25OHD3). DUO samples (n = 12 birds per treatment per day) were collected on days 3, 6, 9, 12, 15, 18, and 21 for cryohistological and immunofluorescence analysis to facilitate the enumeration of the total macrophages, CD80+ macrophages (pro-inflammatory macrophages), and mitotically active cells (BrdU+) to calculate the proportion of proliferating cells (PPC) per duodenal crypt. Bird age impacted crypt PPC with the greatest PPC per duodenal crypt observed on days 3 and 9, and the lowest PPC per crypt was observed on day 21 (P < 0.0001). Broilers from the M25OHD3:PCTL treatment had a greater PPC (P =.002) than birds from the MCTL:PCTL treatment at day 3. An interaction among MDIET and PDIET was observed for proliferating macrophages at day 21 (P = 0.029) where M25OHD3:P25OHD3 birds had more proliferating macrophages than M25OHD3:PCTL-fed birds. These results indicate that combined MDIET and PDIET 25OHD3 supplementation may alter early post-hatch duodenal development and innate immunity.

项与 Multivirus-specific cytotoxic T lymphocytes (mCTLs)(Children's National Research Institute) 相关的新闻（医药）

2023-11-28

·今日头条

肠癌患者福音！全新MCTL细胞治疗结直肠癌国内启动招募，仅限10名

肠癌患者迎来全新一线疗法！解放军总医院正在进行一项MCTL细胞联合CapeOX+贝伐珠单抗一线治疗初始不可根治切除的右半结肠腺癌伴肝转移患者的疗效观察性临床研究，仅限10名，符合条件的患者快申请吧！结直肠癌是全球第三大最常见的癌症，我国结直肠癌发病率居恶性肿瘤第2位，死亡率居第4位，全球负担正在增加，预计 2020 年至2040 年间的发病率将增加56%，达到每年超过 300 万新病例。目前，肠癌的根治手段仍然是手术切除，但大部分患者在确诊时已是晚期，发生了转移，丧失手术机会，传统的放化疗，已经全新的靶向和免疫治疗尽管能够延长生存期，但仍然无法满足临床需求。喜讯！全新MCTL细胞联合CapeOX+贝伐珠单抗一线治疗国内启动招募 MCTL细胞是河北博海生物工程开发有限公司自主研发的个体化、多靶点肿瘤特异性T细胞治疗产品，其核心技术包括：自体外周血肿瘤集群靶标的筛选、肿瘤特异性多肽抗原的制备与鉴定、抗原致敏及体外诱导和培养扩增肿瘤特异性细胞毒T细胞，经静脉回输用以治疗。重要的是，在整个治疗过程中，该技术针对肿瘤免疫逃逸的特性，动态监测患者肿瘤特异性抗原多肽的变化，可及时调整免疫细胞的靶向性。目前该技术的临床研究已获得国家自然科学基金京津冀区域重点项目的支持。其中天津医科大学肿瘤医院生物治疗科任秀宝主任担负的MCTL治疗经二线药物治疗失败的非小细胞肺癌临床研究已经取得可喜结果。由解放军总医院普通外科医学部夏绍友主任负责的“MCTL细胞联合CapeOX+贝伐珠单抗一线治疗初始不可根治切除的右半结肠腺癌伴肝转移患者的临床研究” 已完成301医院医学伦理审查和临床研究注册。本研究拟招募10例初始不可根治切除的右半结肠腺癌伴肝转移患者。希望能够为结直肠癌肝转移患者提供一种个体化、多靶点、肿瘤特异性抗原实时监测的精准免疫细胞治疗策略，以达到控制肿瘤生长，提高根治性手术转化率，延长患者生存期和改善预后的目的。准入标准 1. 经腹部CT检查证实结肠原发灶位于右半结肠(回盲部至横结肠中段)；结肠原发病灶经内镜活检组织病理学诊断为结肠腺癌，包括：乳头状腺癌、管状腺癌、黏液腺癌、印戒细胞癌、未分化癌等； 2. 经腹部CT或MRI检查，明确诊断同时性肝脏转移癌； 3. 既往未接受过化疗，系统性靶向治疗或免疫检查点抑制剂治疗； 4. 年龄:18-75岁； 5. 愿意参加且能够遵守研究方案要求。您的获益 1. 您将得到专业医生的指导和评估； 2. 您将更加明确自身疾病情况，以便进行个性化治疗和各项护理及支持； 3. 您将会有专业医生进行“一对一”随访； 4. 您有可能获得手术的机会； 5. 您有可能延长总体生存期和无进展生存期，并提高生活质量。想寻求MCTL技术及其他国内外治疗新技术帮助，且经济条件允许的情况下，可提交病历至初步评估。结直肠癌已成为暨乳腺癌、肺癌后，全球第三大常见癌症。一旦确诊，早期患者首选的治疗方案是手术，而中晚期结直肠癌最常用的方式是药物治疗。10年前，晚期结直肠癌一旦化疗失败，生命等于进入倒计时。近年来随着基因组测试和精准治疗药物及技术的开发，晚期结直肠癌的生存时间由之前的不到一年提升至3年，并且有20%的患者可以生存5年甚至更长的时间。期待更多国研好药早日获批，落地医保，造福更多国内的肠癌患者！

细胞疗法免疫疗法临床研究

100 项与 Multivirus-specific cytotoxic T lymphocytes (mCTLs)(Children's National Research Institute) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
慢性病	临床1期	美国	Children's Research Institute, Inc.	2014-04-30
机会致病菌感染	临床1期	美国	Children's Research Institute, Inc.	2014-04-30
爱泼斯坦-巴尔病毒感染	临床1期	美国	-	2014-04-01
原发性免疫缺陷疾病	临床1期	美国	-	2014-04-01
腺病毒科感染	临床1期	美国	Children's National Research Institute	2014-02-01
巨细胞病毒感染	临床1期	美国	Children's National Research Institute	2014-02-01

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NEWS 人工标引	临床1期	非小细胞肺癌二线	13	MCTL+特瑞普利单抗	艱廠憲窪簾鹽繭壓繭窪(繭餘簾築艱簾鹹簾壓鹽) = 願衊製餘襯廠糧簾範顧蓋鏇鏇窪築積鹹壓膚夢 (憲醖顧糧齋衊構積鑰齋 ) 更多	积极	2023-12-07