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.

Start Date20 May 2022

Sponsor / Collaborator

Seattle Children's Hospital

[+1]

NCT01994369

/ CompletedPhase 1IIT

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.

Start Date01 May 2014

Sponsor / Collaborator

University of Pennsylvania

NCT02000778

/ CompletedPhase 1IIT

A Pilot & Feasibility Study of the Imaging Potential of EC17 in Subjects Undergoing Intraoperative Detection of Occult Ovarian Carcinoma

The overall prevalence of Ovarian Cancer in the United States according to the US SEER Registry is 182,710 women. Ovarian cancer also has the highest mortality rate of the gynecological cancers. The overall five-year survival rate is 45% and for Stages III and IV it is only 20-25%. The majority of these are aged 50 years or older, but a few girls less than 10 years of age have been diagnosed with ovarian cancer. This risk increases with age and decreases with numbers of pregnancies.
The prognosis for many carcinomas is dependent on the extent of surgical resection. At present, the ability to perform a complete resection with negative margins is limited by the investigator's ability to palpate and visualize the tumor and its borders. In many cases, a more radical resection than necessary is performed in order to provide assurance that negative margins are achieved. This approach may also increase complication rates, as well as short- and long-term morbidity. It is desirable to improve visualization of primary tumors and occult metastases in real time, during surgery. The use of fluorescent probes that recognize cancer-specific antigens, in conjunction with a clinical imaging system, is under investigation.
Ovarian cancer is a prototypic disease for this type of clinical imaging system called intra-operative imaging. Except in Stage IV, the tumors are confined to the pelvis or abdomen and typically involve extensions or implants onto pelvic or abdominal organs or membranes. Tumor debulking surgery is common early in the disease process as many of the tumors can be identified by appearance or feel in the skilled surgeon's hands. The major problems are that tumors can be diffuse and numerous, of various sizes, and often not readily visible in the surgical field.
Over 90-95% of serous ovarian cancers express folate receptor (FR)-alpha, making this receptor an ideal target for marking most ovarian cancers. Folate is the prototypic agonist at the FR-alpha with potential uses for imaging and targeted therapeutic strategies.Chemotherapy does not affect FR-alpha expression in ovarian cancer specimens examined by immunohistochemistry, so prior treatment is unlikely to affect utility of FR-alpha agonists as imaging or therapeutic agents.

Start Date01 Nov 2013

Sponsor / Collaborator

University of Pennsylvania

100 Clinical Results associated with Folate-Fluorescein

100 Translational Medicine associated with Folate-Fluorescein

100 Patents (Medical) associated with Folate-Fluorescein

Literatures (Medical) associated with Folate-Fluorescein

01 Aug 2025·EJSO

Enhancing surgical precision in ovarian cancer with FRα-fluorescence-guided surgery

Review

Author: Scambia, Giovanni ; Ceccaroni, Marcello ; Bogani, Giorgio ; Ferrari, Filippo Alberto ; Francesco, Raspagliesi ; Fagotti, Anna ; Pavone, Matteo ; Bourdel, Nicolas

INTRODUCTION:

Complete cytoreduction is a key prognostic factor in advanced ovarian cancer. Folate receptor alpha (FRα)-targeted intraoperative fluorescence imaging has emerged as a promising tool to enhance identification of tumor localization. Agents like pafolacianine (OTL38) and EC17 improve real-time visualization of malignant lesions, overcoming limitations of conventional methods relying on visual inspection and palpation.

MATERIALS AND METHODS:

we conducted a systematic review to evaluate the safety, efficacy, and feasibility of FRα-targeted fluorescence imaging in ovarian cancer surgery. Studies were identified through comprehensive searches in PubMed, Scopus, and Web of Science. Clinical and preclinical studies assessing FRα-targeted agents with near-infrared or other fluorescence modalities were included. Bias risk was assessed using the Cochrane Risk of Bias Tool for randomized trials and the Newcastle-Ottawa Scale for non-randomized studies.

RESULTS:

Eleven studies, including clinical and preclinical trials, were analyzed. OTL38 significantly improved lesion detection, identifying additional malignant lesions in 33 % of patients undergoing debulking surgery and enhancing detection by 29 % over standard methods, with sensitivity exceeding 85 %. EC17, assessed in smaller studies, identified 16 % more malignant lesions undetected by conventional methods, though autofluorescence was a challenge. Adverse events, predominantly mild, included nausea, vomiting, and transient skin flushing.

CONCLUSIONS:

FRα-targeted imaging may enhance lesion detection during cytoreductive surgery, increasing resection completeness. While EC17 shows feasibility, larger trials support the potential of OTL38. Future research should optimize imaging agents to reduce autofluorescence and assess their impact on survival outcomes.

01 Oct 2022·Annals of surgery

Comparative Experience of Short-wavelength Versus Long-wavelength Fluorophores for Intraoperative Molecular Imaging of Lung Cancer

Article

Author: Sunil Singhal ; Gregory T. Kennedy ; Feredun S. Azari ; Olugbenga Okusanya ; Elizabeth Bernstein ; Jane Keating ; Alix Segil ; Isvita Marfatia ; Ashley Chang ; John C. Kucharczuk ; Andrew Newton ; Azra Din ; Jarrod Predina ; Charuhas Desphande ; Bilal Nadeem

Background::

Intraoperative molecular imaging (IMI) using tumor-targeted optical contrast agents can improve cancer resections. The optimal wavelength of the IMI tracer fluorophore has never been studied in humans and has major implications for the field. To address this question, we investigated 2 spectroscopically distinct fluorophores conjugated to the same targeting ligand.

Methods::

Between December 2011 and November 2021, patients with primary lung cancer were preoperatively infused with 1 of 2 folate receptor-targeted contrast tracers: a short-wavelength folate-fluorescein (EC17; λem=520 nm) or a long-wavelength folate-S0456 (pafolacianine; λem=793 nm). During resection, IMI was utilized to identify pulmonary nodules and confirm margins. Demographic data, lesion diagnoses, and fluorescence data were collected prospectively.

Results::

Two hundred eighty-two patients underwent resection of primary lung cancers with either folate-fluorescein (n=71, 25.2%) or pafolacianine (n=211, 74.8%). Most tumors (n=208, 73.8%) were invasive adenocarcinomas. We identified 2 clinical applications of IMI: localization of nonpalpable lesions (n=39 lesions, 13.8%) and detection of positive margins (n=11, 3.9%). In each application, the long-wavelength tracer was superior to the short-wavelength tracer regarding depth of penetration, signal-to-background ratio, and frequency of event. Pafolacianine was more effective for detecting subpleural lesions (mean signal-to-background ratio=2.71 vs 1.73 for folate-fluorescein, P<0.0001). Limit of signal detection was 1.8 cm from the pleural surface for pafolacianine and 0.3 cm for folate-fluorescein.

Conclusions::

Long-wavelength near-infrared fluorophores are superior to short-wavelength IMI fluorophores in human tissues. Therefore, future efforts in all human cancers should likely focus on long-wavelength agents.

01 Oct 2020·Molecular imaging and biologyQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: 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.

News (Medical) associated with Folate-Fluorescein

15 Jan 2025

·endpts.com

Oncology biotech plots expedited approval for bone cancer drug after Phase 2 win

OS Therapies is moving ahead with plans for an accelerated approval pathway after its off-the-shelf candidate for people who have had surgery to treat osteosarcoma succeeded in a single-arm mid-stage study. The New York-based biotech’s HER2-targeted immunotherapy, dubbed OST-HER2, achieved statistical significance in the Phase 2b primary endpoint of event-free survival (EFS) at 12 months, according to a Wednesday release. The drugmaker’s shares $OSTX were up by around 48% at the start of trading on Wednesday. Around one-third of 39 evaluable subjects aged 12 to 39 with recently resected osteosarcoma with metastases that had recurred in the lungs were free of disease recurrence following treatment with OST-HER2. This compares well with the 20% EFS seen with historical control, according to the drugmaker. In the trial’s secondary survival endpoint, interim results showed 91% of patients given OST-HER2 were still alive at one year compared with 80% for historical control, good for a p-value of 0.07. The data come after OS Therapies announced in October that the final patient in the trial had completed their last visit. A month later, the company secured $6 million in a private placement. The biotech is now planning to engage with the FDA on a potential accelerated approval path for the treatment candidate, CEO Paul Romness said in the release. Romness has previously held roles at Johnson & Johnson, Amgen and Boehringer Ingelheim. There are currently no FDA-approved treatments to prevent recurrent, fully resected, lung metastatic osteosarcoma. The disease often starts in the bones of the legs or arms and affects just 1,000 people in the US each year, but is the most common malignant bone tumor in children and young adults. Around half of all patients are diagnosed with lung metastasis at some point after surgery and chemotherapy, according to OS Therapies. Other drugmakers developing treatments for osteosarcoma include Umoja Biopharma, which is advancing an in vivo CAR-T therapy called UB-TT170 for the disease. Denmark-based ADC biotech Adcendo is homing in on targeting uPARAP , a collagen receptor that’s overexpressed in cancers, including osteosarcoma. Elsewhere, OS Therapies’ OST-HER2 is also being developed for breast cancer and other solid tumors, although a Phase 2a trial in those indications is currently on hold as the company waits for an osteosarcoma approval. The asset is designed to stimulate the body’s immune system to fight cancer better by training HER2-specific T cells to detect and destroy cancer cells. Editor’s note: This article was updated to add the company’s stock movement.

Phase 2Clinical ResultImmunotherapyAccelerated Approval

14 Jan 2025

·www.fiercebiotech.com

Umoja secures $100M series C to bring more CAR-Ts into the clinic

Umoja Biopharma\'s oversubscribed round was led by Double Point Ventures and DCVC Bio.\n Umoja Biopharma has secured $100 million in series C funds as the cancer-focused biotech looks to bring more of its cell therapies into the clinic.Umoja’s only clinical-stage candidate is UB-TT170, a TumorTag-based treatment that tags solid tumor cells that express folate receptor alpha. The asset is being evaluated in a phase 1 trial along with a CAR-T therapy as a treatment for osteosarcoma, the most common type of bone tumor in children.However, Umoja didn’t name-check UB-TT170 in this morning’s release. Instead, the biotech focused on UB-VV400, an off-the-shelf, multidomain fusion protein surface-engineered lentiviral vector designed to generate CD22-directed CAR T cells within a patient’s body. The series C funds will be used to launch clinical studies of UB-VV400 in multiple oncology and autoimmune clinical studies, according to the Jan. 14 release. UB-VV111, a preclinical CD19-focused CAR-T for blood cancers that falls under last year’s collaboration with AbbVie, also received a mention. Both UB-VV400 and UB-VV111 were made with Umoja’s VivoVec platform.Today’s oversubscribed round was led by Double Point Ventures and DCVC Bio, with participants including ARK Invest, Cormorant Asset Management, MPM Capital, Qiming Venture Partners USA, RTW Investments, Alexandria Venture Investments and SoftBank Vision Fund 2, to name a few.“We are pleased to announce the closing of our series C financing with tremendous support from both new and existing investors who recognize Umoja’s potential to develop the industry’s first in vivo CAR T cell generating therapies—all in the hopes of increasing effectiveness, reducing barriers, and expanding access to CAR T cell therapies,” Umoja CEO Andrew Scharenberg, M.D., said in a statement.Umoja emerged in 2020 with $53 million and a mission to push past the limits of today’s immunotherapies. The company raised another $210 million the following year to fund the start of its clinical ambitions.

ImmunotherapyCell TherapyPhase 1

14 Jan 2025

·endpts.com

Umoja’s $100M Series C will advance its bid for more convenient cell therapies

In the 10th megaround of 2025, Umoja Biopharma has banked $100 million in a Series C fundraise with an eye to advancing its pipeline of in vivo CAR-T cell therapies for cancer and autoimmune diseases. The Seattle-based biotech said its candidates help the body make its own cancer-killing cells in contrast to the traditional method of collecting and engineering cells outside the body before delivering them back to the patient. This approach could help avoid long waits for treatment, supply chain constraints and toxicities associated with lymphodepleting chemotherapy, according to the company. Umoja’s CD22-targeting program, UB-VV400, is currently in IND-enabling studies for non-Hodgkin lymphoma and autoimmune conditions. It is one of several programs the Series C proceeds will help fund, according to a Tuesday release . That release didn’t mention Umoja’s only clinical-stage candidate, UB-TT170, which is in Phase 1 development for osteosarcoma. In August 2024, the FDA gave Umoja the green light to dose the first patient with its AbbVie-partnered candidate, UB-VV111, which targets CD19 for blood cancer. The biotech could get up to $1.44 billion in milestones under the terms of a pair of deals it inked with AbbVie in January 2024. Back in 2021, Umoja started work on a manufacturing facility for its in vivo CAR-T cell therapies, supported by a $210 million Series B raise. The company launched in 2020 with $53 million in Series A funding. Double Point Ventures and DCVC Bio co-led the Series C raise, with contributions from SoftBank Vision Fund 2, ARK Invest and CaaS Capital, among others.

Cell TherapyPhase 1Immunotherapy

100 Deals associated with Folate-Fluorescein

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Renal Cell Carcinoma	Phase 2	United States	Endocyte, Inc.	01 Jun 2007
Bone metastases	Phase 1	United States	Endocyte, Inc.	01 Sep 2005

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05312411 (ENLIGHTen-01, SITC2024)	Phase 1	Refractory Osteosarcoma folate receptor (FR)-Î± \| FRÎ²	10	CAR adaptor molecule UB-TT170 (FITC-E2 CAR-T cells)	pmrxwqhlfq(tapzivhfmq) = nujtmesuwa jtgvqvuzvy (fanlurrcfy, 56.1 - 96.4) View more	Positive	05 Nov 2024
NCT01511055 (CTgov)	Phase 2	Ovarian Cancer	27	EC-17	jacycgvkub = filsuzgwrn uazkkybait (cbkyoeaukb, buwzxrfoji - vkhjgxxysn) View more	-	14 Oct 2020
ASCO2008	Phase 1	Metastatic Renal Cell Carcinoma	11	EC90 vaccine	nbizakonbr(jrlzgbippx) = izciehdtso lztowwpyhi (hmdvntwmcb )	-	20 May 2008
ASCO2008	Phase 1	Metastatic Renal Cell Carcinoma	11	EC17 folate-targeted therapy	nbizakonbr(jrlzgbippx) = gkqzcnqiot lztowwpyhi (hmdvntwmcb )	-	20 May 2008

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