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Methods of treating cancer and infectious diseases using cell based therapies

A technology of cell and in vitro cell culture, applied in the human field, can solve problems such as aging

Active Publication Date: 2018-11-09
EMORY UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, T cells are considered senescent if they have limited proliferative potential in response to antigenic stimulation

Method used

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  • Methods of treating cancer and infectious diseases using cell based therapies
  • Methods of treating cancer and infectious diseases using cell based therapies
  • Methods of treating cancer and infectious diseases using cell based therapies

Examples

Experimental program
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[0085] VIP signaling regulates alloantigen-induced T cell proliferation

[0086] To explore the role of VIP signaling in the allogeneic immune response, a one-way mixed lymphocyte reaction (MLR) containing VIP and / or antagonist VIPhyb peptides was performed. Addition of VIP decreased luciferase T cell proliferation in a dose-dependent manner, while addition of VIPhyb increased T cell proliferation. VIPhyb reversed the inhibitory effect of VIP in MLR, restoring T cell proliferation to higher levels than control cultures.

[0087] Pharmacological blockade during ex vivo T cell expansion for CAR T manufacturing increases yield and preserves naive and central memory compartments

[0088]Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell malignancy that primarily affects older patient populations. Despite robust treatment options, a subset of patients with DLBCL have lymphomas that are highly resistant to treatment. Because the disease in these patients is refractory ...

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Abstract

This disclosure relates to compositions and methods of reversing senescence in T cells by interrupting vasoactive intestinal peptide (VIP) signalling and / or inhibiting phosphatidylinositol- 3 -kinase(PI3 kinase) inhibitor signalling and uses in managing cancer and chronic viral infections. In certain embodiments, the disclosure contemplates methods of reversing T cell senescence by mixing T cellin vitro with an agent that prevents VIP from interacting with VIP receptors and / or a PI3 Kinase inhibitor. In certain embodiments, the disclosure contemplates the expansion of senescent T cells by mixing with a PI3 kinase inhibitor, an agent that block VIP and VIP receptor signalling, a VIP degrading enzyme, and combinations thereof.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims the benefit of US Provisional Application No. 62 / 319,957, filed April 8, 2016. The entire contents of this application are hereby incorporated by reference for all purposes. [0003] Statement Regarding Federally Funded Research [0004] This invention was made with government support under RO1HL116737-01A and RO1CA188523 awarded by the National Institutes of Health. The US Government has certain rights in this invention. [0005] Incorporation of references for materials submitted as text documents through the Office Electronic Filing System (EFS-WEB) [0006] The Sequence Listing related to this application is provided in text format in lieu of a paper copy, and is incorporated into this specification by reference. The name of the text file containing the sequence listing is 16094PCT_ST25.txt. The text file is 11KB, created on April 5, 2017, and submitted electronically via EFS-Web. Backgrou...

Claims

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Application Information

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IPC IPC(8): A61K38/16A61K38/17A61K39/395A61K39/12A61K38/54A61K35/14A61K35/28A61K38/22A61K45/06C07K16/28
CPCC12N5/0636C12N2501/515C12N2501/51C12N2501/727C12N2501/35C12N5/0638A61K39/4611A61K39/4644A61K39/4631A61K2239/48A61K39/464838A61K2300/00A61K45/06A61K38/208A61K38/482A61K38/4886C12Y304/21039C12Y304/24011A61K39/39A61P35/00A61P31/00A61K38/22A61K38/54A61K35/17C12N2501/05A61K35/28C07K16/28
Inventor 埃德蒙·沃勒安娜·莫里斯克里斯多佛·彼得森李建明瑞玛·潘吉瓦尼李静霞
Owner EMORY UNIVERSITY
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