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Compositions and methods for treating cancer
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A composition and technology for cancer, applied in the field of compositions and methods for treating cancer, can solve problems such as troubles, affecting the quality of life, etc.
Pending Publication Date: 2021-10-29
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For example, administering PARP inhibitors to patients either orally or intravenously is associated with symptoms such as nausea and fatigue, which can be extraordinarily troublesome and affect quality of life
and may require discontinuation of PARP inhibitors
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Embodiment 1
[0116] Example 1 - Cancer Treatment Paradigms
[0117] A combination therapy comprising chemotherapeutics, drug-resistant γδ T cells, PARP-1 inhibitors, and immune checkpoint inhibitors is used to treat cancer patients. For the treatment of ovarian cancer, niraparib, olaparib, or rucaparib are PARP inhibitors. For the treatment of glioblastoma, olaparib or niraparib as PARP inhibitors. The chemotherapeutic agent is selected from alkylating agents (such as cyclophosphamide, ifosfamide), metabolic antagonists (such as methotrexate (MTX), 5-fluorouracil or its derivatives), antineoplastic antibiotics (such as Mitomyces adriamycin), plant-derived antineoplastic agents (e.g., vincristine, vindesine, Paclitaxel, Abraxane), cisplatin, carboplatin, etoposide, etc. Such agents may further include, but are not limited to, the anticancer agent trimethoxybenzoate (TMTX); temozolomide; raltitrexed; S-(4-nitrobenzyl)-6-thioinosine (NBMPR);6 - benzylguanidine (6-BG), dichloronitrosourea...
Embodiment 2
[0127] Example 2 - Expression of stress ligands on glioma cell lines when exposed to a combination of PARP inhibitor (PARPi) and Temozolomide (TMZ)
[0128] Materials and methods
[0129] Methods of cell collection / handling / culture conditions
[0130] The general strategy for developing treatment options is outlined below. With the goal of generating the total number of γδ T cells needed to treat a patient, the initial dose is administered as a freshly prepared cell population.
[0131] After patient augmentation, a single 2-volume apheresis was performed immediately after resection and before initiation of induction chemotherapy / radiotherapy.
[0132] exist Bioreactor with 2.0×10 6 The MNC expansion culture was initiated at a concentration of 1 / ml, determined by a validated procedure, and maintained in an OpTimizer (Life Technologies) 5% CO 2 , 37° C. + 5 μgM zoledronic acid (Novartis Oncology; East Hanover, NJ) + 50 U / ml IL-2 (Miltenyi; Duarte, CA). Cultures were ma...
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Abstract
The invention provides combination therapies for treating cancer comprising compositions and methods for [gamma][delta]T cell immunotherapy in combination DDR inhibitors, including but not limited to PARP inhibitors. Preferably, the combination of [gamma][delta]T cell immunotherapy and PARP inhibitors for the treatment of cancer further includes combinations with other immunotherapies such as immune checkpoint (ICP) blockade therapy and / or DNA damaging agents such as cytotoxic chemotherapeutic agents. Preferably, when the combination of [gamma][delta]T cell immunotherapy and DDR inhibitor therapy further include chemotherapeutic agents, the [gamma][delta]T cells are genetically modified to impart resistance to the chemotherapeutic agent.
Description
[0001] related application [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 757,383, filed November 8, 2018. The entire content of the above application is incorporated herein by reference. Background technique [0003] Gamma-delta (γδ) T cells are an important subset of T lymphocytes because they can recognize multiple antigens without antigen priming and the presence of major histocompatibility complex (MHC) molecules. They can attack target cells directly through cytotoxic activity or indirectly through the activation of other immune cells. The functional response of γδ T cells is induced by a variety of factors, including the recognition of stress antigens, which promote the production of cytokines that regulate pathogen clearance, inflammation, and stress in tissue homeostasis. [0004] Subpopulations of human γδ T cells all exhibit cytotoxic potential, which is induced by, for example, the expression of cell surface receptors [i.e. ...
Claims
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