A Phase I Feasibility And Safety Study of Fluorescein-Specific (FITC-Ew) CAR T Cells In Combination With Parenterally Administered Folate-Fluorescein (UB-TT170) For Osteogenic Sarcoma

The purpose of this study is to see if a new treatment could help patients who have osteosarcoma that does not go away with treatment (is refractory) or comes back after treatment (is recurrent).This study is testing a combination of study therapies, UB-TT170 and genetically modified chimeric antigen receptor T lymphocyte (CAR T) cells, which work together in a way that is different from chemotherapy.
In this study, researchers will take some of your blood and remove the T cells in a process called "apheresis". Then the T cells are taken to a lab and changed to CAR T cells that recognize the flags from UB-TT170. Once researchers think they have grown enough CAR T cells, called antiFL(FITC-E2) CAR T cells, to fight your cancer, you may get some chemotherapy to make room in your body for the new cells and then have those cells put back in your body.
A few days after the you get your CAR T cell infusion you will start to get infusions of UB-TT170, with the dose slowly increasing for the first few infusions until you have reached a maximum dose that you will get on a regular schedule. The UB-TT170 will attach to your tumor cells and flag them so that they attract the CAR T cells. When the CAR T cells see the labeled tumor cells they can kill the tumor cells.
The active part of the study lasts about 8 months, and if you get the CAR T cell infusion you will be in long-term follow-up for 15 years.

开始日期2022-05-20

申办/合作机构

Seattle Children's Hospital

[+1]

NCT01994369 / Completed临床1期IIT

A Pilot & Feasibility Study of the Imaging Potential of EC17 in Subjects Undergoing Surgery Presenting Breast Cancer

Breast cancer is the most common cancer and the second cause of cancer mortality in women. There are approximately 200,000 new cases of breast cancer a year. Classically, breast cancers are divided into two groups, invasive and non-invasive. A mainstay of the treatment of both of these types is surgical resection not only for therapeutic purposes but also for diagnostic purposes. Breast conserving therapy includes surgical lumpectomy and post-operative radiation. However, despite best surgical practices, when patients undergo BCT anywhere from 20 - 40% of these patients have margins positive for cancer. This leads to increased rates of reoperation which are quoted to be as high as 30% and increased local recurrences.
There is an over expression of folate receptors located on the surface of many human carcinoma nodules.Specifically for breast cancer up to 33% of all breast cancers over express the folate receptor.
Folate-fluorescein isothiocyanate, or folate-FITC, also identified as EC-17, targets folate receptors over expressed in certain cancers such as breast cancer, and could help in better identifying the margins of the cancer thereby achieving negative margins.

开始日期2014-05-01

申办/合作机构

University of Pennsylvania

NCT01996072 / Completed临床1期IIT

A Pilot & Feasibility Study of the Imaging Potential of EC17 in Subjects Undergoing Parathyroidectomy for Primary Hyperparathyroidism.

Primary hyperparathyroidism is a significant medical and public health problem in the world and affects approximately 100,000 new patients in the United States alone. If left untreated this can lead to renal stones, osteoporosis, fatigue, and depression. The best treatment for primary hyperparathyroidism is surgical parathyroidectomy. However surgical parathyroidectomy can be difficult due to the variant location of the parathyroid glands. Up to 5% of patients leave the operating room without surgical cure.
Primary hyperparathyroidism is an ideal disease to investigate intraoperative fluorescent imaging. This would allow surgeons to identify the parathyroid glands and resect the suspicious parathyroid glands. Folate receptor (FR) has been found to be over-expressed in parathyroid tissue and not thyroid issues. An ideal surgical treatment would combine FR-specific fluorescent tracers with intraoperative imaging. It is important to note that FR is expressed only in the proximal tubules of the kidneys, activated macrophages, and in the choroidal plexus. Thus, the false positive detection rate is expected to be extremely low.
A group well known to us in the Netherlands has completed a pilot study utilizing a folate-FITC conjugate in 12 patients with ovarian cancer. Another group of investigators in Mayo have subsequently performed this study on 20 more patients without any serious adverse events (personal communication). They report excellent sensitivity and specificity with this technique with only grade 1 side effects (allergic reaction). All side effects reversed when the injection was halted. Patients with a history of allergic reactions to insect bites should not participate (fluorescein is derived from the firefly insect, folate is an essential vitamin).
A fluorescent contrast agent (folate-FITC or EC17) will be used to determine if it will localize to the primary tumor nodule(s) or mass(es) of patients undergoing parathyroid surgery.

开始日期2013-11-01

申办/合作机构

University of Pennsylvania

100 项与 Folate-Fluorescein 相关的临床结果

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100 项与 Folate-Fluorescein 相关的转化医学

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100 项与 Folate-Fluorescein 相关的专利（医药）

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项与 Folate-Fluorescein 相关的文献（医药）

2020-10-01·Molecular imaging and biology3区 · 医学

Fluorescence Labeling of Circulating Tumor Cells with a Folate Receptor-Targeted Molecular Probe for Diffuse In Vivo Flow Cytometry

3区 · 医学

Article

作者: Srinivasarao, Madduri ; Amiji, Mansoor M ; Patil, Roshani A ; Niedre, Mark ; Low, Philip S

PURPOSE:

We recently developed a new instrument called "diffuse in vivo flow cytometry" (DiFC) for enumeration of rare fluorescently labeled circulating tumor cells (CTCs) in small animals without drawing blood samples. Until now, we have used cell lines that express fluorescent proteins or were pre-labeled with a fluorescent dye ex vivo. In this work, we investigated the use of a folate receptor (FR)-targeted fluorescence molecular probe for in vivo labeling of FR+ CTCs for DiFC.

PROCEDURES:

We used EC-17, a FITC-folic acid conjugate that has been used in clinical trials for fluorescence-guided surgery. We studied the affinity of EC-17 for FR+ L1210A and KB cancer cells. We also tested FR- MM.1S cells. We tested the labeling specificity in cells in culture in vitro and in whole blood. We also studied the detectability of labeled cells in mice in vivo with DiFC.

RESULTS:

EC-17 showed a high affinity for FR+ L1210A and KB cells in vitro. In whole blood, 85.4 % of L1210A and 80.9 % of KB cells were labeled above non-specific background with EC-17, and negligible binding to FR- MM.1S cells was observed. In addition, EC-17-labeled CTCs were readily detectable in circulation in mice with DiFC.

CONCLUSIONS:

This work demonstrates the feasibility of labeling CTCs with a cell-surface receptor-targeted probe for DiFC, greatly expanding the potential utility of the method for pre-clinical animal models. Because DiFC uses diffuse light, this method could be also used to enumerate CTCs in larger animal models and potentially even in humans.

2019-09-03·Molecular pharmaceutics2区 · 医学

Detecting Functional and Accessible Folate Receptor Expression in Cancer and Polycystic Kidneys

2区 · 医学

Article

作者: Vaughn, Jeremy F. ; Reddy, Joseph A. ; Wang, Emilia Z. ; Vlahov, Iontcho R. ; Leamon, Christopher P. ; Shillingford, Jonathan M. ; Chu, Haiyan ; Felten, Albert E. ; Westrick, Elaine ; Xu, Le-Cun ; Nelson, Melissa ; Parker, Nikki ; Lu, Yingjuan J.

Folate-based small molecule drug conjugates (SMDCs) are currently under development and have shown promising preclinical and clinical results against various cancers and polycystic kidney disease. Two requisites for response to a folate-based SMDC are (i) folate receptor alpha (FRα) protein is expressed in the diseased tissues, and (ii) FRα in those tissues is accessible and functionally competent to bind systemically administered SMDCs. Here we report on the development of a small molecule reporter conjugate (SMRC), called EC2220, which is composed of a folate ligand for FRα binding, a multilysine containing linker that can cross-link to FRα in the presence of formaldehyde fixation, and a small hapten (fluorescein) used for immunohistochemical detection. Data show that EC2220 produces a far greater IHC signal in FRα-positive tissues over that produced with EC17, a folate-fluorescein SMRC that is released from the formaldehyde-denatured FRα protein. Furthermore, the extent of the EC2220 IHC signal was proportional to the level of FRα expression. This EC2220-based assay was qualified both in vitro and in vivo using normal tissue, cancer tissue, and polycystic kidneys. Overall, EC2220 is a sensitive and effective reagent for evaluating functional and accessible receptor expression in vitro and in vivo.

2018-02-01·Molecular imaging and biology3区 · 医学

Standardization and Optimization of Intraoperative Molecular Imaging for Identifying Primary Pulmonary Adenocarcinomas

3区 · 医学

Article

作者: Singhal, Sunil ; Predina, Jarrod D ; Okusanya, Olugbenga ; D Newton, Andrew ; Low, Philip

PURPOSE:

Intraoperative molecular imaging (IMI) is an emerging technology used to locate pulmonary adenocarcinomas and identify positive margins during surgery. Background noise and tissue autofluorescence have been major obstacles. The goal of this study is to optimize the image quality of folate receptor alpha (FRα) targeted IMI for pulmonary adenocarcinomas by modifying emission data.

PROCEDURES:

A total of 15 lung cancer patients were enrolled in a pilot study. In the first cohort, FRα upregulation within pulmonary adenocarcinoma tumors was confirmed by analyzing specimens from five pulmonary adenocarcinoma patients with flow cytometry and immunohistochemistry. Next, in a cohort of five additional patients, autofluorescence of intrathoracic structures and tissues was quantified. Lastly, five patients with tumors at various depths from the pleural surface were enrolled and received the FRα-targeted optical contrast agent, EC17. In this final cohort, resected pulmonary adenocarcinomas were imaged at a wide range of fluorescence exposure times (0 to 200 ms), various laser powers, and with unique filter configurations. Tumor-to-noise ratio (TNR) for images was generated using region of interest software.

RESULTS:

Pulmonary adenocarcinomas highly express FRα. Significant autofluorescence from native thoracic tissues was found with the highest fluorescent signals at the bronchial stump (547 ± 98, range 423-699), the pulmonary artery (267 ± 64, range 200-374), and cortical bone (266 ± 17, range 243-287). High levels of autofluorescence were appreciated after systemic administration of EC17; however, TNR was improved by altering exposure settings at the time of the imaging. Optimal fluorescent exposure time occurs at 40 ms (25 frames/s).

CONCLUSIONS:

Exposure properties can be manipulated to maximize TNR thus allowing for successful intraoperative detection of pulmonary adenocarcinomas during surgery. Optimization of the conditions for intraoperative molecular imaging sets the stage for future clinical trials utilizing targeted IMI techniques which can aid the surgeon at the time of cancer resection.

项与 Folate-Fluorescein 相关的新闻（医药）

2024-10-04

·GlobeNewswire-Health Care

Umoja Biopharma Announces Poster Presentations at the 39th Annual Meeting of the Society for Immunotherapy of Cancer

SEATTLE, Oct. 04, 2024 (GLOBE NEWSWIRE) -- Umoja Biopharma, Inc. (Umoja), a transformative immunotherapy company creating off-the-shelf treatments that aim to extend the reach and effectiveness of CAR-T cell therapies in oncology and autoimmunity, today announced that Umoja will present two poster presentations at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), being held November 6-10, 2024, in Houston, Texas and virtually. Umoja’s poster presentations will focus on preclinical data of UB-VV400, an off-the-shelf, multidomain fusion (MDF) protein surface engineered lentiviral vector designed to generate CD22-directed CAR T cells in vivo without requiring lymphodepleting chemotherapy, as well as the company’s RACR-induced cytotoxic lymphocytes (iCIL) platform and its potential for increased production and persistence of CAR T cells. Details of the poster presentations can be found below: Presentation Title: Development of a Surface Engineered Lentiviral Vector for In Vivo Generation of CD22-Directed CAR T CellsPresenting Author: Jeffrey Teoh, Ph.D.Poster Number: 1145Presentation Date/Time: Friday, November 8, 2024; Poster Hall Hours: 9 am – 7 pm CT Presentation Title: Arming pluripotent stem cell-derived lymphocytes with a suite of synthetic receptors enables scalable manufacturing and enhanced persistence and potency for potential off-the-shelf immunotherapyPresenting Author: Dillon Jarrell, Ph.D.Poster Number: 272Presentation Date/Time: Saturday, November 9, 2024; Poster Hall Hours: 9 am – 8:30 pm CT In addition to Umoja’s poster presentations, Seattle Children’s Therapeutics, Umoja’s collaboration partner will be presenting early experience data from the ENLIGHTen-01 trial of UB-TT170. Details of the poster presentation can be found below: Presentation Title: Early Experience on ENLIGHTen-01: A Phase 1 Study of Bispecific Adapter Molecule-Controlled Folate Receptor CAR T-Cell Therapy for Relapsed/Refractory OsteosarcomaPresenting Author: Catherine Albert, M.D.Poster Number: 233Presentation Date/Time: Friday, November 8, 2024; Poster Hall Hours: 9 am – 7 pm CT About Umoja BiopharmaUmoja Biopharma, Inc. is a clinical-stage biotechnology company aiming to develop off-the-shelf therapeutics that improve the reach, effectiveness, and access of CAR-T cell therapies in both oncology and autoimmunity. Umoja’s VivoVec™ in vivo gene delivery technology empowers a patient’s own immune system to fight disease. Enabling its core technology is the Company’s state-of-the-art lentiviral vector development and manufacturing facility in Louisville, Colorado. Umoja believes its approach can provide broader access and improved effectiveness of the most advanced immunotherapies, enabling more patients to live better, fuller lives. To learn more, connect with Umoja on LinkedIn and visit http://umoja-biopharma.com/. InvestorsStephen JasperGilmartin Group, LLCstephen@gilmartinir.com MediaMatt Wright Real Chemistrymwright@realchemistry.com

免疫疗法细胞疗法临床1期

2023-09-08

·药明康德

速递 | 体内制造CAR-T细胞获概念验证，可直接改造40~60%的循环T细胞

▎药明康德内容团队编辑Umoja Biopharma宣布，该公司体内生成CAR-T细胞疗法的VivoVec技术平台在一项非人灵长类动物（NHP）研究中，有效和持久地生成CAR-T细胞，并表现出良好的耐受性。CAR-T细胞已经在治疗多种血液癌症方面表现出惊人的疗效，给患者带来治愈的希望。然而目前的CAR-T细胞疗法制造方式复杂，需要从患者体内分离T细胞，在体外进行基因工程改造，再输注回患者体内。整个过程耗时耗力，是限制CAR-T疗法可及性的重要原因之一。Umoja Biopharma的VivoVec技术平台通过将称为VivoVec颗粒的第三代慢病毒载体技术，直接在患者体内生成靶向肿瘤的CAR-T细胞，这一“现货型”技术省去了与体外制造CAR-T细胞疗法相关的繁琐过程，有望提高CAR-T细胞疗法的可及性。这次公布的数据包括正在进行的研究中接受治疗的前4只NHP的结果，结果显示在不给予预处理淋巴细胞耗竭化疗的情况下，单次输注Umoja的VivoVec颗粒后，CD20靶向CAR-T细胞快速有效地在体内生成。此外，这些数据表明体内产生的CAR-T细胞表现出靶向活性和持续性的T细胞记忆。关键性结果包括：VivoVec单次给药后，体内产生了靶向CD20的CAR-T细胞，CAR-T细胞扩增的峰值水平出现在第7-10天之间。靶向CD20的CAR-T细胞表现出靶向活性，导致持久的B细胞再生障碍性贫血。在接受计划临床剂量和未接受预处理化疗的3只动物中，CD20 CAR阳性细胞峰值约占循环T细胞总量的40-60%，包括证实的中央记忆T细胞应答。在第1只动物中，第30天后观察到额外的独立CAR-T细胞扩增。没有观察到与VivoVec给药相关的毒性。大家都在看作为药明康德旗下专注于细胞和基因疗法的CTDMO，药明生基致力于加速和变革基因和细胞治疗及其他高端治疗的开发、测试、生产和商业化。药明生基能够助力全球客户将更多创新疗法早日推向市场，造福病患。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] Umoja's in vivo CAR-T therapy shows positive first signs in primates. Retrieved September 6, 2023, from https://www.fiercebiotech.com/research/umojas-vivo-car-t-therapy-shows-positive-first-signs-primates[2] Umoja Biopharma’s VivoVec Platform Presents Encouraging Proof-of-Concept Data in Ongoing Non-Human Primate Study at the 8th CAR-TCR Summit. Retrieved September 6, 2023, from https://www.umoja-biopharma.com/news/umoja-biopharmas-vivovec-platform-presents-encouraging-proof-of-concept-data-in-ongoing-non-human-primate-study-at-the-8th-car-tcr-summit/免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

细胞疗法免疫疗法基因疗法

2023-09-05

·FierceBiotech

Umoja's in vivo CAR-T therapy shows positive first signs in primates

Umoja Biopharma’s technology is designed to overcome the key limitations of CAR-T therapy, eventually making it possible to have “off-the-shelf” CAR-Ts that are more accessible to patients. Umoja Biopharma’s VivoVec platform has generated in vivo chimeric antigen receptor T cells, or CAR-T cells, in nonhuman primates, according to new data presented by the company Sept. 1 during the annual CAR-TCR Summit in Boston. The CAR-Ts also appeared to have activity against target cells and continued proliferating for more than a month in one of the animals. "Our hope is that the replication of these data in our early clinical trials will lead to a new class of in vivo CAR-T cell therapeutics that expand the breadth of reach of CAR-T cell therapies by reducing costs and logistical complexity of delivery and by offering an immediate, off-the-shelf, product that generates autologous, patient-specific CAR-T cells," Andy Scharenberg, M.D., Umoja's co-founder and CEO, told Fierce Biotech Research via email. Umoja’s technology programs a patient's T cells against their cancer in vivo—that is, without ever having to remove the T cells from their body, as currently approved therapies require, or transferring them from donors as occurs with next-generation allogeneic therapies like Allogene's. Instead, Umoja uses lipid nanoparticles it's dubbed VivoVec particles to activate, integrate and express the CAR in a patient’s own T cells. This replaces the expensive, time-consuming process of extracting and transducing the cells with CARs using viral vectors before re-implanting them back into the patient, steps that can be marred by vector shortages and the possibility of manufacturing failure or low yields. The platform also negates the need for chemotherapy to clear out a patient’s blood cells. Back in May at the American Society of Gene & Cell Therapy’s annual conference, Umoja reported preclinical data on VivoVec in mice. In the new studies, the researchers injected four male and female pigtail macaque monkeys in the groin-area lymph nodes with a single, clinically relevant dose of the VivoVec particles designed to generate anti-CD20 CARs, the type used to target B-cell lymphoma. The team then monitored the animals for CAR-T cell activation and expansion as well as toxicity. None of the monkeys received chemotherapy beforehand. In three of the primates, CD20 CAR-T cells peaked at about 40% to 60% of total circulating T cells at their peak. The same three monkeys also had persistent B-cell aplasia, a sign that the CAR-Ts were working. The numbers for most of the animals exceeded the benchmark for ex vivo CAR-T therapies in a similar primate model, Scharenberg told Fierce. In a 2018 study on rhesus macaque monkeys that underwent chemotherapy followed by CAR-T infusion, the engineered cells proliferated to a peak of 272 to 4,450 CAR-T cells per microliter; their B-cell aplasia lasted between 35 and 42 days. In Umoja's latest study, the CAR-T cells in two of the monkeys peaked at between 5,000 and 10,000 cells per microliter and their B-cell aplasia lasted beyond 42 days. In another, the researchers detected a large secondary CAR-T cell expansion around Day 49 or 50, "suggesting that VivoVec may capture aspects of memory T cell biology that are difficult or impossible to capture with ex vivo CAR-T cell manufacturing processes," Scharenberg wrote. While the therapy was largely well tolerated, there were a few side effects in two of the animals—though none out of the ordinary for CAR-T therapy, and less serious than what was seen in the 2018 study on an ex vivo treatment. The most serious was a mild cytokine release syndrome and neurotoxicity event that culminated in a single seizure, to which the monkey responded to single doses of the appropriate medications. The primate experiments are ongoing; more data from them will be presented at medical conferences in the fall, Umoja said in the release. The company currently has a piece of its technology in clinical trials at Seattle Children’s Hospital and plans to submit a request to the FDA in the first half of 2024 to take its first VivoVec-based therapy into human studies. Editor's note: This story has been updated to clarify the technology in clinical trials at Seattle Children's Hospital and the timeline for submitting a request for its first VivoVec-based therapy.

细胞疗法免疫疗法ASH会议

100 项与 Folate-Fluorescein 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
转移性肾细胞癌	临床2期	美国	Endocyte, Inc.	2007-06-01
肿瘤转移	临床1期	美国	Endocyte, Inc.	2005-09-01

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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


NCT01511055 (CTgov)	临床2期	卵巢癌	27	EC-17	鑰網遞窪鑰製築齋簾鑰(觸簾鹽選鏇齋顧淵範窪) = 糧壓觸鬱鑰顧壓艱構鬱積壓餘壓鏇窪餘鏇繭窪 (築淵窪簾構鬱構願淵遞, 膚夢醖獵遞製鏇鏇憲繭 ~ 鏇膚願獵廠獵夢襯繭艱) 更多	-	2020-10-14
ASCO2008	临床1期	转移性肾细胞癌	11	EC90 vaccine	築範範醖網膚範壓製齋(簾鬱選衊鏇膚艱鏇範窪) = 鬱構構憲構願廠築壓鹽鏇觸鹽構窪網製簾網範 (膚鬱鏇簾鑰衊憲網淵廠 )	-	2008-05-20
ASCO2008	临床1期	转移性肾细胞癌	11	EC17 folate-targeted therapy	築範範醖網膚範壓製齋(簾鬱選衊鏇膚艱鏇範窪) = 蓋願製淵構襯製蓋範壓鏇觸鹽構窪網製簾網範 (膚鬱鏇簾鑰衊憲網淵廠 )	-	2008-05-20