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公开(公告)号：US09782463B2
公开(公告)日：2017-10-10
申请号：US15041642
申请日：2016-02-11
Applicant: Immunovative Thearpies, Ltd.
Inventor： Michael Har-Noy
IPC: A61K35/28 , A61K35/26 , A61K39/00 , C12N5/0783 , A61K35/17
CPC classification number: A61K39/0005 , A61K35/17 , A61K2039/5154 , A61K2039/57 , C12N5/0636 , C12N2501/51 , C12N2501/515 , C12N2531/00 , C12N2533/40
Abstract: A method of manipulating allogeneic cells for use in allogeneic cell therapy providing a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism, or “Mirror Effect”. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the “mirror” of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The “mirror” of the GVH effect is the host vs. graft (HVG) effect The anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used to stimulate host immunity in a complete HLA mis-matched setting in a patient.
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公开(公告)号：US09320794B2
公开(公告)日：2016-04-26
申请号：US13796171
申请日：2013-03-12
Applicant: Immunovative Therapies Ltd.
Inventor： Michael Har-Noy
CPC classification number: A61K41/0028 , A61B18/02 , A61B18/12 , A61K35/17 , A61K39/0011 , A61K39/39 , A61K2039/5158 , A61K2039/55511 , A61K2039/57 , Y02A50/412 , Y02A50/484
Abstract: The disclosure herein relates generally to immunotherapy and, more specifically, to the use of immunotherapy for treating tumors and pathogen infected tissues. The immunotherapy relates to first priming patients with allogeneic cells designed to be rejected by a Th1 mediated mechanism, then inducing in situ necrosis or apoptosis in a tumor or pathogen infected lesion. Necrosis or apoptosis can be induced by methods such as cryotherapy, irreversible electroporation, chemotherapy, radiation therapy, ultrasound therapy, ethanol chemoablation, microwave thermal ablation, radiofrequency energy or a combination thereof applied against at least a portion of the tumor or pathogen infected tissue. One or more doses of allogeneic cells (e.g., Th1 cells) are then delivered within or proximate to the tumor or pathogen-infected tissue in the primed patient. The present invention provides an immunotherapeutic strategy to develop de-novo systemic (adaptive) immunity to a tumor or pathogen.
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公开(公告)号：US09301977B2
公开(公告)日：2016-04-05
申请号：US14173494
申请日：2014-02-05
Applicant: Michael Har-Noy
Inventor： Michael Har-Noy
IPC: A61K35/28 , A61K35/26 , A61K35/17 , C12N5/0783 , A61K39/00
CPC classification number: A61K39/0005 , A61K35/17 , A61K2039/5154 , A61K2039/57 , C12N5/0636 , C12N2501/51 , C12N2501/515 , C12N2531/00 , C12N2533/40
Abstract: A method of manipulating allogeneic cells for use in allogeneic cell therapy providing a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism, or “Mirror Effect”. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the “mirror” of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The “mirror” of the GVH effect is the host vs. graft (HVG) effect The anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used to stimulate host immunity in a complete HLA mis-matched setting in a patient.
Abstract translation: 一种操作同种异体细胞用于同种异体细胞治疗的方法，其提供高活性同种异体T细胞的组合物，其被输注到免疫活性癌症患者中以引发新的抗肿瘤免疫机制，或“镜效应”。 与当前的同种异体细胞治疗方案相反，其中移植物中的T细胞介导有益的移植物抗肿瘤（GVT）和有害的移植物抗宿主（GVH）效应，本发明的同种异体细胞刺激宿主T细胞介导 这些效果的“镜子”。 GVT效应的镜子是宿主与肿瘤（HVT）的作用。 GVH效应的“镜子”是宿主与移植物（HVG）的作用。抗肿瘤HVT效应与无毒的HVG排斥反应有关。 本发明的高度激活的同种异体细胞可以用于在患者的完全HLA不匹配的设置中刺激宿主免疫。
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公开(公告)号：US20140178334A1
公开(公告)日：2014-06-26
申请号：US14193832
申请日：2014-02-28
Applicant: Immunovative Therapies, Ltd.
Inventor： Michael Har-Noy
Abstract: This invention relates to compositions and methods for immunotherapy of cancer. Specifically, a method of cancer immunotherapy is described which results in the systemic liquidation of both solid and metastatic tumors whereever they reside in the body. The compositions include activated allogeneic Th1 cells that when administered appropriately lead to liquidation of tumors. The method includes administering priming doses of the therapeutic composition, ablation of a selected tumor lesion along with intratumoral injection of the composition and then infusion of the therapeutic composition. These steps enable the systemic liquidation of tumors secondary to immune cell infiltration and leads to immune-mediated tumor eradication.
Abstract translation: 本发明涉及癌症免疫治疗的组合物和方法。 具体地，描述了一种癌症免疫治疗方法，其导致无论身体存在于固体和转移性肿瘤中的系统性清除。 组合物包括活化的同种异体Th1细胞，其当被适当地施用导致肿瘤的清除时。 该方法包括施用引发剂量的治疗组合物，消融所选择的肿瘤损伤以及肿瘤内注射组合物，然后输注治疗组合物。 这些步骤使得免疫细胞浸润继发的肿瘤的系统性清除并导致免疫介导的肿瘤根除。
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公开(公告)号：US20130052212A1
公开(公告)日：2013-02-28
申请号：US13596142
申请日：2012-08-28
Applicant: Michael Har-Noy
Inventor： Michael Har-Noy
CPC classification number: A61K39/0005 , A61K35/17 , A61K2039/5154 , A61K2039/57 , C12N5/0636 , C12N2501/51 , C12N2501/515 , C12N2531/00 , C12N2533/40
Abstract: A method of manipulating allogeneic cells for use in allogeneic cell therapy providing a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism, or “Mirror Effect”. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the “mirror” of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The “mirror” of the GVH effect is the host vs. graft (HVG) effect. The anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used to stimulate host immunity in a complete HLA mis-matched setting in a patient.
Abstract translation: 一种操作同种异体细胞用于同种异体细胞治疗的方法，其提供高度激活的同种异体T细胞的组合物，其被输注到免疫活性癌症患者中以引发新的抗肿瘤免疫机制或镜效应。 与当前的同种异体细胞治疗方案相比，其中移植物中的T细胞介导有益的移植物抗肿瘤（GVT）和有害的移植物抗宿主（GVH）效应，本发明的同种异体细胞刺激宿主T细胞介导 这些效果的镜子。 GVT效应的镜子是宿主与肿瘤（HVT）的作用。 GVH效应的镜子是宿主与移植物（HVG）的作用。 抗肿瘤HVT效应与无毒的HVG排斥反应有关。 本发明的高度激活的同种异体细胞可以用于在患者的完全HLA不匹配的设置中刺激宿主免疫。
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Patent Agency Ranking
公开(公告)号：US20120045423A1
公开(公告)日：2012-02-23
申请号：US13214534
申请日：2011-08-22
Applicant: Michael Har-Noy
Inventor： Michael Har-Noy
IPC: A61K35/14 , A61P35/00 , C12N5/0783
CPC classification number: C12N5/0636 , A61K35/17 , A61K2039/5158 , A61K2039/57 , C12N5/0638 , C12N2501/51 , C12N2501/515
Abstract: A novel cell type has been generated that has both Th1 characteristics and cytolytic activity. These Th1/killer cells are CD4+ cells purified from peripheral blood and manipulated to have Th1 characteristics such as production of IFN-gamma combined with cytolytic activity similar to cytotoxic T-cells (CTL). The CTL activity is targeted toward diseased cells, not normal cells. The cytolytic activity of the Th1/killer cells is mediated by Granzyme B-Perforin mechanism and results in apoptotic death of diseased cells. Methods of producing and using these Th1/killer cells include isolating CD4+ cells from peripheral blood, activating the CD4+ T-cells to form Th1/killer cells and administering these Th1/killer cells with the cytolytic activity to a patient wherein the Th1/killer cells are allogeneic to the patient.
Abstract translation: 已经产生了具有Th1特征和溶细胞活性的新型细胞类型。 这些Th1 /杀伤细胞是从外周血纯化的CD4 +细胞，并被操作以具有Th1特征，例如与细胞毒性T细胞（CTL）类似的细胞溶解活性结合的IFN-γ的产生。 CTL活性靶向患病细胞，而不是正常细胞。 Th1 /杀伤细胞的细胞溶解活性由Granzyme B-Perforin机制介导，导致患病细胞的凋亡死亡。 产生和使用这些Th1 /杀伤细胞的方法包括从外周血分离CD4 +细胞，激活CD4 + T细胞以形成Th1 /杀伤细胞，并向患者施用具有溶细胞活性的这些Th1 /杀伤细胞，其中Th1 /杀伤细胞 与患者同种异体。
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公开(公告)号：US20110250173A1
公开(公告)日：2011-10-13
申请号：US13084900
申请日：2011-04-12
Applicant: Michael Har-Noy
Inventor： Michael Har-Noy
CPC classification number: A61K39/0011 , A61K35/17 , A61K38/1774 , A61K38/217 , A61K39/39 , A61K2035/122 , A61K2035/124 , A61K2039/5156 , A61K2039/5158 , A61K2039/57 , C12N5/0637 , C12N2502/1114 , A61K2300/00
Abstract: The present invention relates to methods of suppressing the immune tolerance of a disease or disease antigens in a patient. The method also promotes the activity of the effector T lymphocytes. The invention includes administering a therapeutic composition that promotes a Th1 environment in the patient while decreasing the immunosuppressive activity of Treg cells that can lead to disease antigen tolerance and immunoavoidance of the disease antigens by the patient. The therapeutic composition includes allogeneic emTh-1 cells. The therapeutic composition can also include disease antigens such as the chaperone-rich cell lysate of the disease antigen.
Abstract translation: 本发明涉及抑制患者中疾病或疾病抗原的免疫耐受性的方法。 该方法还促进效应T淋巴细胞的活性。 本发明包括施用在患者中促进Th1环境的治疗组合物，同时降低Treg细胞的免疫抑制活性，其可以导致患者的疾病抗原抗性和疾病抗原的免疫吸收。 治疗组合物包括同种异体emTh-1细胞。 治疗组合物还可以包括疾病抗原，例如疾病抗原的富含分子伴侣的细胞裂解物。
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公开(公告)号：US20110033435A1
公开(公告)日：2011-02-10
申请号：US12887054
申请日：2010-09-21
Applicant: Michael Har-Noy
Inventor： Michael Har-Noy
CPC classification number: A61K39/0005 , A61K35/17 , A61K2039/5154 , A61K2039/57 , C12N5/0636 , C12N2501/51 , C12N2501/515 , C12N2531/00 , C12N2533/40
Abstract: The composition of activated CD4 cells is derived from a healthy human donor. The composition from the healthy human donor is suspended in an infusion media and packaged in a vehicle for administration to a subject to treat disease.
Abstract translation: 活化的CD4细胞的组成来自健康的人供体。 来自健康人供体的组合物悬浮在输注介质中并包装在载体中用于给予受试者以治疗疾病。
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公开(公告)号：US20110028912A1
公开(公告)日：2011-02-03
申请号：US12887039
申请日：2010-09-21
Applicant: Michael Har-Noy
Inventor： Michael Har-Noy
CPC classification number: A61K39/0005 , A61K35/17 , A61K2039/5154 , A61K2039/57 , C12N5/0636 , C12N2501/51 , C12N2501/515 , C12N2531/00 , C12N2533/40
Abstract: A method for formulating T-cells for use as a medicant comprises activating the T-cells by incubating the T-cells in a nutrient culture media with an activating agent. The T-cells together with the activating agent are suspended in a media suitable for infusion. The activated T-cells are packaged together with the activating agent in a container suitable for administration to a patient.
Abstract translation: 用于配制用作药物的T细胞的方法包括通过将营养培养基中的T细胞与活化剂一起孵育来活化T细胞。 将T细胞与活化剂一起悬浮在适于输注的培养基中。 活化的T细胞与活化剂一起包装在适于给予患者的容器中。
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公开(公告)号：US20050214274A1
公开(公告)日：2005-09-29
申请号：US11069010
申请日：2005-03-01
Applicant: Michael Har-Noy
Inventor： Michael Har-Noy
IPC: A61K35/12 , A61K45/00 , A61M31/00 , C12N5/0783
CPC classification number: C12N5/0636 , A61K2035/124 , C12N2531/00 , C12N2533/40
Abstract: Ex-vivo prepared T-cells are harvested from cell culture conditions and formulated in medium suitable for infusion. The formulation is made by labeling the cells with one or more agents which have reactivity for T-cell surface moieties capable of delivery activation signals upon cross-linking and mixing the labeled cells with biodegradable nanospheres or microspheres coated with a material capable of cross-linking the agents attached to the T-cell surface moieties. Alternatively, the formulation may be made by mixing a population of T-cells with biodegradable nanospheres or microspheres coated with a first material and one or more second materials. The first material binds the second material and the second material has reactivity for surface moieties on the T-cells and the interaction of the second materials with the T-cells causes the activation of the T-cells. In either method, the mixture of T-cells and biodegradable spheres are suspended in a medium suitable for infusion, and the mixture is packaged in a container.
Abstract translation: 从细胞培养条件收获离体制备的T细胞，并在适于输注的培养基中配制。 通过用一种或多种对一种或多种具有反应性的试剂标记细胞来制备所述制剂，所述试剂在交联并且将标记的细胞与可交联的材料涂覆的可生物降解的纳米球或微球体混合后，能够产生传递激活信号的T细胞表面部分具有反应性 附着于T细胞表面部分的试剂。 或者，可以通过将一组T细胞与可生物降解的纳米球或涂覆有第一材料和一种或多种第二材料的微球混合来制备制剂。 第一种材料结合第二种材料，而第二种材料对T细胞上的表面部分具有反应性，第二种材料与T细胞的相互作用导致T细胞的激活。 在任一方法中，将T细胞和可生物降解的球体的混合物悬浮在适于输注的培养基中，并将混合物包装在容器中。
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