-
公开(公告)号:US20200046768A1
公开(公告)日:2020-02-13
申请号:US16536948
申请日:2019-08-09
Applicant: University Health Network
Inventor: Li Zhang , Dalam Ly , Linan Fang
Abstract: Methods for the treatment of cancer using double negative T cells (DNTs) and a PD-1 or PD-L1 inhibitor are described. Tumors treated with DNTs and a PD-1 inhibitor exhibited increased DNT cell infiltration and increased cytotoxicity towards non-small cell lung cancer (NSCLC) cells. Also described are compositions and kits comprising DNTs and a PD-1 or PD-L1 inhibitor and their use for the treatment of cancer.
-
公开(公告)号:US09925220B2
公开(公告)日:2018-03-27
申请号:US14674548
申请日:2015-03-31
Applicant: University Health Network
Inventor: Li Zhang , Mei Han , Pouneh Dokouhaki
IPC: C12N5/0783 , A61K35/17
CPC classification number: A61K35/17 , C12N5/0636 , C12N2501/23 , C12N2501/2302 , C12N2501/2304 , C12N2501/515
Abstract: A method of expanding double negative T cells in culture is described. The method comprises (a) providing a starting sample comprising DN T cells or precursors thereof; (b) substantially depleting CD8+ and CD4+ T cells from the starting sample; (c) culturing the sample from step (b) with an immobilized T cell mitogen in a culture medium comprising an agent that can stimulate DN T cell growth (d) washing the cells obtained in step (c) and resuspending in a culture medium comprising the agent without the T cell mitogen; and (e) washing the cells obtained in step (d) and resuspending in a culture medium comprising the agent and a soluble T cell mitogen. The DN T cells obtained by the method are useful in a variety of applications including the treatment of cancer, infectious diseases, graft versus host disease and autoimmune disease.
-
公开(公告)号:US20230011889A1
公开(公告)日:2023-01-12
申请号:US17782071
申请日:2020-12-07
Applicant: University Health Network
Inventor: Li Zhang , Jong Bok Lee , Daniel Vasic , Ismat Khatri , Dalam Ly , Yuki Sze Long Leung
IPC: A61K35/17 , C07K14/725 , C12N5/0783 , A61P35/00
Abstract: The disclosure relates to the development and use of CD4− CD8− double negative T (DNT) cells genetically modified to bind to one or more target antigens to enhance DNT cell anti-cancer activity such as with a chimeric antigen receptor (CAR). Genetically modified DNT cells can be generated ex vivo and expanded from allogeneic healthy donor cells and used as off-the-shelf therapy to overcome allogeneic graft-versus-host disease (GvHD) and/or host-versus-graft rejection in the treatment of cancer.
-
公开(公告)号:US10517937B2
公开(公告)日:2019-12-31
申请号:US15503916
申请日:2015-08-17
Applicant: University Health Network
Inventor: Li Zhang , Jong Bok Lee , Branson Chen
IPC: A61K35/17 , A61K39/00 , A61K31/7068
Abstract: Methods for the treatment of cancer using double negative (DN) T cells are described. The DNTs may be used for the treatment of chemotherapy-resistant cancers such as recurring or relapsing acute myeloid leukemia (AML). The use of allogenic DNTs, such as those derived from healthy donors, that do not exhibit toxicity towards normal host tissues and the complications associated with graft-versus-host-disease, is also described.
-
公开(公告)号:US20230059785A1
公开(公告)日:2023-02-23
申请号:US17797630
申请日:2021-02-08
Applicant: University Health Network
Inventor: Li Zhang , Jongbok Lee , Aaron David Schimmer
IPC: A61K35/17 , A61K31/635 , A61P35/00
Abstract: Methods of treating T cells with Venetoclax to increase T cell-mediated cytotoxicity and/or T cell mediated anti-tumor activity are described. Also described are populations of enhanced T cells as well as associated methods and uses for the treatment of cancer.
-
公开(公告)号:US20220073877A1
公开(公告)日:2022-03-10
申请号:US17415957
申请日:2019-12-19
Applicant: University Health Network
Inventor: Li Zhang , Jong Bok Lee , Hyeonjeong Kang
IPC: C12N5/0783 , A01N1/02 , A61K35/17 , A61K35/15 , A61K39/395 , C07K16/28 , A61K35/28
Abstract: Described are methods for the production and use of cryopreservable double negative T cells (DNTs) for the treatment of cancer as an off-the-shelf cellular therapy. A sample population of DNTs is expanded using DNTs from one or more donors. The expanded population of DNTs from different donors does not exhibit alloreactivity against allogenic cells in the expanded population. The expanded populations of DNTs can be long-term stored as cryopreserved products.
-
公开(公告)号:US10201572B2
公开(公告)日:2019-02-12
申请号:US15266756
申请日:2016-09-15
Applicant: UNIVERSITY HEALTH NETWORK
Inventor: Li Zhang , Jong Bok Lee
Abstract: There is provided herein methods of treating leukemia or lymphoma in a subject in need thereof, with double negative T cells (DNTs) in combination with Interferon-γ.
-
公开(公告)号:US20160045550A1
公开(公告)日:2016-02-18
申请号:US14674548
申请日:2015-03-31
Applicant: University Health Network
Inventor: Li Zhang , Mei Han , Pouneh Dokouhaki
IPC: A61K35/17 , C12N5/0783
CPC classification number: A61K35/17 , C12N5/0636 , C12N2501/23 , C12N2501/2302 , C12N2501/2304 , C12N2501/515
Abstract: A method of expanding double negative T cells in culture is described. The method comprises (a) providing a starting sample comprising DN T cells or precursors thereof; (b) substantially depleting CD8+ and CD4+ T cells from the starting sample; (c) culturing the sample from step (b) with an immobilized T cell mitogen in a culture medium comprising an agent that can stimulate DN T cell growth (d) washing the cells obtained in step (c) and resuspending in a culture medium comprising the agent without the T cell mitogen; and (e) washing the cells obtained in step (d) and resuspending in a culture medium comprising the agent and a soluble T cell mitogen. The DN T cells obtained by the method are useful in a variety of applications including the treatment of cancer, infectious diseases, graft versus host disease and autoimmune disease.
Abstract translation: 描述培养培养中双阴性T细胞的方法。 该方法包括(a)提供包含DN T细胞或其前体的起始样品; (b)从起始样品中大量消耗CD8 +和CD4 + T细胞; (c)在包含可以刺激DN T细胞生长的试剂的培养基中培养来自步骤(b)的来自步骤(b)的样品的固定化的T细胞丝裂原,(d)洗涤步骤(c)中获得的细胞并重新悬浮于培养基中,所述培养基包含 没有T细胞有丝分裂原的药剂; 和(e)洗涤步骤(d)中获得的细胞,并重新悬浮于包含该试剂和可溶性T细胞丝裂原的培养基中。 通过该方法获得的DN T细胞可用于各种应用,包括治疗癌症,感染性疾病,移植物抗宿主病和自身免疫性疾病。
-
公开(公告)号:US11534460B2
公开(公告)日:2022-12-27
申请号:US15573379
申请日:2016-05-11
Applicant: UNIVERSITY HEALTH NETWORK
Inventor: Li Zhang , Paulina Achita , Jong Lee , Dalam Ly , Dzana Dervovic
IPC: A61K35/17 , C12N5/0783 , A61P35/00
Abstract: There is provided herein a method for expanding human CD4-CD8- regulatory T cells (DN Tregs) from a population of cells comprising DN Tregs, comprising: culturing the population of cells with artificial antigen presenting cells (APCs), preferably the DN Tregs are αβ-TCR-CD56- or alternatively γ8-TCR+.
-
-
-
-
-
-
-
-