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

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100 Clinical Results associated with Fluorescein-Specific CAR T Cells(Umoja Biopharma, Inc.)

100 Translational Medicine associated with Fluorescein-Specific CAR T Cells(Umoja Biopharma, Inc.)

100 Patents (Medical) associated with Fluorescein-Specific CAR T Cells(Umoja Biopharma, Inc.)

Literatures (Medical) associated with Fluorescein-Specific CAR T Cells(Umoja Biopharma, Inc.)

01 Jan 2024·Clinical & Translational Immunology

Endogenous bystander killing mechanisms enhance the activity of novel FAP‐specific CAR‐T cells against glioblastoma

Article

Author: Polara, Ruhi ; Gargett, Tessa ; Pitson, Stuart M ; Yu, Wenbo ; Bonder, Claudine S ; Truong, Nga Th ; Cockshell, Michaelia P ; Brown, Michael P ; Tea, Melinda N ; Ebert, Lisa M

AbstractObjectivesCAR‐T cells are being investigated as a novel immunotherapy for glioblastoma, but clinical success has been limited. We recently described fibroblast activation protein (FAP) as an ideal target antigen for glioblastoma immunotherapy, with expression on both tumor cells and tumor blood vessels. However, CAR‐T cells targeting FAP have never been investigated as a therapy for glioblastoma.MethodsWe generated a novel FAP targeting CAR with CD3ζ and CD28 signalling domains and tested the resulting CAR‐T cells for their lytic activity and cytokine secretion function in vitro (using real‐time impedance, flow cytometry, imaging and bead‐based cytokine assays), and in vivo (using a xenograft mimicking the natural heterogeneity of human glioblastoma).ResultsFAP‐CAR‐T cells exhibited target specificity against model cell lines and potent cytotoxicity against patient‐derived glioma neural stem cells, even when only a subpopulation expressed FAP, indicating a bystander killing mechanism. Using co‐culture assays, we confirmed FAP‐CAR‐T cells mediate bystander killing of antigen‐negative tumor cells, but only after activation by FAP‐positive target cells. This bystander killing was at least partially mediated by soluble factors and amplified by IL‐2 which activated the non‐transduced fraction of the CAR‐T product. Finally, a low dose of intravenously administered FAP‐CAR‐T cells controlled, without overt toxicity, the growth of subcutaneous tumors created using a mixture of antigen‐negative and antigen‐positive glioblastoma cells.ConclusionsOur findings advance FAP as a leading candidate for clinical CAR‐T therapy of glioblastoma and highlight under‐recognised antigen nonspecific mechanisms that may contribute meaningfully to the antitumor activity of CAR‐T cells.

01 Nov 2023·Biochemical and Biophysical Research Communications

F77 antigen is a promising target for adoptive T cell therapy of prostate cancer

Article

Author: Leferovich, John ; Wentz, Tyra ; Bagchi, Atrish ; Nunez-Cruz, Selene ; Grover, Payal ; Milone, Michael C ; Greene, Mark I

Adoptive immunotherapy using chimeric antigen receptor (CAR) T cells has made significant success in treating hematological malignancies, paving the way for solid tumors like prostate cancer. However, progress is impeded by a paucity of suitable target antigens. A novel carbohydrate antigen, F77, is expressed on both androgen-dependent and androgen-independent prostate cancer cells, making it a potential immunotherapy target. This study entails the generation and evaluation of a second-generation CAR against a carbohydrate antigen on malignant prostate cancer cells. Using a single chain fragment variable (scFv) from an F77-specific mouse monoclonal antibody, we created second-generation CARs with CD28 and CD137 (4-1BB) costimulatory signals. F77 expressing lentiviral CAR T cells produce cytokines and kill tumor cells in a F77 expression-dependent manner. These F77-specific CAR T cells eradicate prostate tumors in a human xenograft model employing PC3 cells. These findings validate F77 as a promising immunotherapeutic target for prostate cancer and other malignancies with this aberrant carbohydrate structure.

01 Aug 2023·Journal for ImmunoTherapy of Cancer

Targeting sphingosine 1-phosphate receptor 3 inhibits T-cell exhaustion and regulates recruitment of proinflammatory macrophages to improve antitumor efficacy of CAR-T cells against solid tumor

Article

Author: Zhang, Benxia ; Liao, Weiting ; He, Xia ; Qin, Diyuan ; Wang, Yongsheng ; Ma, Qizhi ; Gao, Ge ; Shu, Pei

BackgroundsChimeric antigen receptor (CAR)-modified T cells (CAR-T) are limited in solid tumors due to the hostile tumor microenvironment (TME). Combination therapy could be a promising approach to overcome this obstacle. Recent studies have shown that sphingosine 1-phosphate receptor (S1PR)3 has tremendous potential in regulating the immune environment. However, the functional significance of S1PR3 in T-cell-based immunotherapies and the molecular mechanisms have not been fully understood.MethodsHere, we studied the combination of EpCAM-specific CAR T-cell therapy with pharmacological blockade of S1PR3 against solid tumor. We have applied RNA sequencing, flow cytometry, ELISA, cellular/molecular immunological technology, and mouse models of solid cancers.ResultsOur study provided evidence that S1PR3 high expression is positively associated with resistance to programmed cell death protein-1 (PD-1)-based immunotherapy and increased T-cell exhaustion. In addition, pharmacological inhibition of S1PR3 improves the efficacy of anti-PD-1 therapy. Next, we explored the possible combination of S1PR3 antagonist with murine EpCAM-targeted CAR-T cells in immunocompetent mouse models of breast cancer and colon cancer. The results indicated that the S1PR3 antagonist could significantly enhance the efficacy of murine EpCAM CAR-T cells in vitro and in vivo. Mechanistically, the S1PR3 antagonist improved CAR-T cell activation, regulated the central memory phenotype, and reduced CAR-T cell exhaustion in vitro. Targeting S1PR3 was shown to remodel the TME through the recruitment of proinflammatory macrophages by promoting macrophage activation and proinflammatory phenotype polarization, resulting in improved CAR-T cell infiltration and amplified recruitment of CD8+T cells.ConclusionsThis work demonstrated targeting S1PR3 could increase the antitumor activities of CAR-T cell therapy at least partially by inhibiting T-cell exhaustion and remodeling the TME through the recruitment of proinflammatory macrophages. These findings provided additional rationale for combining S1PR3 inhibitor with CAR-T cells for the treatment of solid tumor.

100 Deals associated with Fluorescein-Specific CAR T Cells(Umoja Biopharma, Inc.)

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Indication	Highest Phase	Country/Location	Organization	Date
Osteosarcoma	Phase 1	US	Umoja Biopharma, Inc.Startup	20 May 2022

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