Development of Natural Killer (NK) Cell Line-Derived Extracellular Vesicles as a New Treatment for Cancer
开发自然杀伤 (NK) 细胞系衍生的细胞外囊泡作为癌症的新治疗方法
基本信息
- 批准号:10383462
- 负责人:
- 金额:$ 39.96万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-04-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:ADME StudyAllogenicAutologousBehaviorBlood - brain barrier anatomyBlood Chemical AnalysisBody WeightBone PainCell CountCell DeathCell LineCell ProliferationCell TherapyCellsCessation of lifeCharacteristicsChemoresistanceClinical ResearchClinical effectivenessCombined Modality TherapyControl GroupsDataDevelopmentDiagnosisDiseaseDisease remissionFreezingFutureGenerationsGoalsGrowthHealthcareHematologic NeoplasmsHematopoieticHistocompatibilityHospital ReferralsHourHumanImmune systemImmunodeficient MouseImmunohistochemistryImmunotherapeutic agentImmunotherapyIn VitroIndividualInfectionInfusion proceduresInterleukin-12Interleukin-15Interleukin-2KidneyKnowledgeLaboratoriesLeadManaged Care ProgramsMeasuresMedical OncologistMembraneMetabolicModalityModelingMultiple MyelomaMusNatural Killer CellsNatural ProductsNeoplasm MetastasisNormal CellOrganOrgan WeightOutcomePainParticle SizePatientsPharmaceutical PreparationsPhasePreparationPrimary Health CareProductionProteinsRNARecurrenceRefractoryRefractory DiseaseRelapseResidual NeoplasmResistanceRouteSalesSmall Business Technology Transfer ResearchStable DiseaseStem cell transplantStructureSurvival RateSymptomsTestingTherapeuticTissuesToxic effectVariantblood groupcancer cellcancer stem cellcancer therapycancer typecell killingchemotherapycohortcommercial applicationcytokinecytokine release syndromeexperimental groupextracellular vesiclesgraft vs host diseasehuman modelimprovedinnovationloss of functionmouse modelnanoparticleneoplastic cellpatient advocacy grouppre-clinicalpreventprotein expressionside effecttechnological innovationtertiary caretumortumor hypoxiatumor microenvironment
项目摘要
Vanquish Bio is an immunotherapy company reimagining treatment of cancer with the use of unique natural
killer (NK) cell derived extracellular vesicles (EVs). The goal of this STTR is to develop a therapy using natural
products of the immune system for targeted destruction of myeloma tumor cells. Multiple myeloma (MM)
represents ~10% of hematological cancers, and there were ~32,110 new cases and ~12,960 deaths in the
U.S. in 2019. Despite treatments that include stem cell transplantation and/or chemotherapy, patients
inevitably relapse. New innovations are needed that extend survival, increase durability of remission and
provide options to patients ineligible for front-line therapy. We developed NK3.3, a human NK cell line derived
from a healthy donor. These cells kill an array of tumor types. Using a minimal residual disease mouse model
of human MM, administration of NK3.3 EVs prevented tumor recurrence for up to 100 days, versus 21 days
without treatment. As NK3.3 grow in culture, they release EVs as small membrane-bound structures that are
also capable of killing many different tumor cells without harming normal cells. NK3.3 EVs also kill cancer stem
cells (CSC); these are resistant to standard chemotherapy and responsible for metastasis and recurrence. NK
EVs can be produced in large quantities, frozen, stored and then thawed, without loss of function. Other
advantages of using NK3.3 EVs include: 1) resistance to the hypoxic tumor microenvironment, 2) ability to
cross the blood-brain barrier, 3) stability and 4) low toxicity. EVs are not restricted by blood group or
histocompatibility and are therefore an immunotherapeutic modality that can be a universal treatment. Our goal
is to develop a new infusion therapy product that will improve survival rates with less side effects for MM
patients with relapsed/refractory or stable disease.
Phase I is to generate NK3.3-derived EVs and demonstrate efficacy against MM and extend durability of
remission, with minimal, toxic side effects.
Specific Aim 1: Identify activators that maximize tumor killing activity of NK3.3 EVs. NK EVs will be
isolated from NK3.3 cells cultured with activating cytokines IL-2, IL-12 and IL-15 individually and in
combinations. Our goal is to prepare NK EVs that kill ≥90% of tumor cells within 72 hours of treatment, with
less than 10% normal cell death.
Specific Aim 2: Determine proof-of-concept efficacy with low toxicity of NK EVs in MM-bearing
immunodeficient mice. We will administer different concentrations of NK EVs in MM-bearing immunodeficient
mice with stable disease. The goal is to extend remission beyond 21 days in ≥50% of mice. Toxicity will be
measured for qualitative visible signs and behavior, and quantitative variation in body weight, organ weight and
blood chemistry. We will prove feasibility of producing more potent NK EV preparations with anti-MM activity
and proof-of-concept oriented efficacy and toxicity data of NK EV therapy against MM.
Vanquish Bio是一家免疫治疗公司,利用独特的天然药物,
杀伤(NK)细胞衍生的细胞外囊泡(EV)。该STTR的目标是开发一种使用天然药物的治疗方法,
用于骨髓瘤肿瘤细胞的靶向破坏的免疫系统的产物。多发性骨髓瘤(MM)
占血液系统癌症的约10%,其中约32,110例新发病例和约12,960例死亡。
美国2019年尽管治疗包括干细胞移植和/或化疗,
不可避免地复发。需要新的创新来延长生存期,增加缓解的持久性,
为不符合一线治疗条件的患者提供选择。我们开发了NK 3.3,一种人类NK细胞系,
一个健康的捐赠者这些细胞杀死一系列肿瘤类型。使用微小残留病小鼠模型
在人MM中,施用NK3.3 EV预防肿瘤复发长达100天,而不是21天。
没有治疗。当NK3.3在培养物中生长时,它们释放EV作为小的膜结合结构,
也能够杀死许多不同的肿瘤细胞而不伤害正常细胞。NK3.3电动汽车也能杀死癌症干细胞
细胞(CSC);这些细胞对标准化疗有抗性,并导致转移和复发。NK
电动汽车可以大量生产,冷冻,储存,然后解冻,而不会失去功能。其他
使用NK3.3EV的优点包括:1)对缺氧肿瘤微环境的抗性,2)
穿过血脑屏障,3)稳定性和4)低毒性。电动汽车不受血型或
组织相容性,因此是一种可以作为通用治疗的免疫疗法。我们的目标
是开发一种新的输液治疗产品,将提高生存率,减少副作用的MM
复发性/难治性或稳定性疾病患者。
I期是产生NK3.3衍生的EV,并证明对MM的疗效和延长
缓解,最小的毒副作用。
具体目标1:鉴定使NK3.3 EV的肿瘤杀伤活性最大化的活化剂。NK EV将成为
分离自分别用活化细胞因子IL-2、IL-12和IL-15培养的NK 3.3细胞,
组合。我们的目标是制备在治疗72小时内杀死≥90%肿瘤细胞的NK EV,
少于10%的正常细胞死亡。
具体目标2:确定NK EV在MM携带者中的低毒性概念验证疗效
免疫缺陷小鼠我们将在携带MM的免疫缺陷小鼠中施用不同浓度的NK EV。
病情稳定的小鼠。目标是在≥50%的小鼠中将缓解期延长至21天以上。毒性将是
测量定性可见体征和行为,以及体重、器官重量和
血液化学我们将证明生产具有抗MM活性的更有效的NK EV制剂的可行性
以及针对MM的NK EV疗法的概念验证导向的功效和毒性数据。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JACKI KORNBLUTH其他文献
JACKI KORNBLUTH的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JACKI KORNBLUTH', 18)}}的其他基金
Molecular Characterization of Anti-Tumor Activity Mediated by Extracellular Vesicles Derived from Natural Killer Cells
自然杀伤细胞来源的细胞外囊泡介导的抗肿瘤活性的分子表征
- 批准号:
10587355 - 财政年份:2023
- 资助金额:
$ 39.96万 - 项目类别:
Analysis of NKLAM: A Novel Gene Associated With Cellular Cytotoxicity
NKLAM 分析:与细胞毒性相关的新基因
- 批准号:
8413781 - 财政年份:2012
- 资助金额:
$ 39.96万 - 项目类别:
Analysis of NKLAM: A Novel Gene Associated With Cellular Cytotoxicity
NKLAM 分析:与细胞毒性相关的新基因
- 批准号:
8696768 - 财政年份:2012
- 资助金额:
$ 39.96万 - 项目类别:
NKLAM: An RBR E3 Ubiquitin Ligase Essential for Regulation of Innate Immunity
NKLAM:一种 RBR E3 泛素连接酶,对于调节先天免疫至关重要
- 批准号:
9898218 - 财政年份:2012
- 资助金额:
$ 39.96万 - 项目类别:
Analysis of NKLAM: A Novel Gene Associated With Cellular Cytotoxicity
NKLAM 分析:与细胞毒性相关的新基因
- 批准号:
8795661 - 财政年份:2012
- 资助金额:
$ 39.96万 - 项目类别:
Analysis of NKLAM: A Novel Gene Associated With Cellular Cytotoxicity
NKLAM 分析:与细胞毒性相关的新基因
- 批准号:
8243104 - 财政年份:2012
- 资助金额:
$ 39.96万 - 项目类别:
PLATELET-ACTIVATING FACTOR AND METASTASIS: CALCIUM-INDEPENDENT PHOSPHOLIPASE
血小板激活因子和转移:钙非依赖性磷脂酶
- 批准号:
8361461 - 财政年份:2011
- 资助金额:
$ 39.96万 - 项目类别:
Role of Natural Killer Lytic-Associated Molecule (NKLAM) in Natural Killer Functi
自然杀伤裂解相关分子 (NKLAM) 在自然杀伤功能中的作用
- 批准号:
8123617 - 财政年份:2010
- 资助金额:
$ 39.96万 - 项目类别:
NKLAM--A NOVEL GENE REQUIRED FOR NK FUNCTION
NKLAM--NK 功能所需的新型基因
- 批准号:
2103280 - 财政年份:1993
- 资助金额:
$ 39.96万 - 项目类别:
NKLAM--A NOVEL GENE REQUIRED FOR NK FUNCTION
NKLAM--NK 功能所需的新型基因
- 批准号:
2103282 - 财政年份:1993
- 资助金额:
$ 39.96万 - 项目类别:
相似海外基金
HLA-homozygous iPSC-cardiomyocytE Aggregate manufacturing technoLogies for allogenic cell therapy to the heart (HEAL)
HLA-纯合 iPSC-心肌细胞 用于心脏同种异体细胞治疗 (HEAL) 的聚集体制造技术
- 批准号:
10039902 - 财政年份:2022
- 资助金额:
$ 39.96万 - 项目类别:
EU-Funded
Evaluation of the efficacy of LAT1 inhibitor to tumor stroma and immunity in an allogenic mouse model of colon cancer having abundant stroma.
在具有丰富基质的同种异体结肠癌小鼠模型中评估 LAT1 抑制剂对肿瘤基质和免疫的功效。
- 批准号:
21K15925 - 财政年份:2021
- 资助金额:
$ 39.96万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Mechanism of kidney injury associated with graft-versus-host disease after allogenic stem cell transplantation
同种异体干细胞移植后移植物抗宿主病相关肾损伤的机制
- 批准号:
21K08410 - 财政年份:2021
- 资助金额:
$ 39.96万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Clarification of the origin and maintenance mechanisms of junctional epithelium and identification of its stem cells using allogenic tooth germ transplantation
阐明交界上皮的起源和维持机制并利用同种异体牙胚移植鉴定其干细胞
- 批准号:
20K21672 - 财政年份:2020
- 资助金额:
$ 39.96万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
The study about the allogenic MSCs transplantation to the cardiac disease models.
同种异体间充质干细胞移植至心脏病模型的研究。
- 批准号:
18K16395 - 财政年份:2018
- 资助金额:
$ 39.96万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Artificial nerves containing allogenic basal lamellae scaffold and bone marrow derived stem cells
含有同种异体基底板层支架和骨髓干细胞的人工神经
- 批准号:
17K10951 - 财政年份:2017
- 资助金额:
$ 39.96万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Role of HSP90-alpha in preserving immunoprivilege of allogenic mesenchymal stem cells in the ischemic heart
HSP90-α 在保护缺血心脏同种异体间充质干细胞免疫特权中的作用
- 批准号:
370541 - 财政年份:2017
- 资助金额:
$ 39.96万 - 项目类别:
Operating Grants
Attempt to Prefabricate Vascularized Allogenic Bone in Recipient -Use of Cultured Bone Marrow Cells-
尝试在受者体内预制血管化的同种异体骨 - 使用培养的骨髓细胞 -
- 批准号:
16K10863 - 财政年份:2016
- 资助金额:
$ 39.96万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Allogenic micobiota-reconstitution (AMR) for the treatment of patients with diarhea-predominant irritable bowel syndrome (IBS-D) - the AMIRA trial
同种异体微生物群重建 (AMR) 用于治疗腹泻型肠易激综合征 (IBS-D) 患者 - AMIRA 试验
- 批准号:
276706135 - 财政年份:2015
- 资助金额:
$ 39.96万 - 项目类别:
Clinical Trials
Induction of thyme epithelial cells from iPS cells and application to allogenic transplantation
iPS细胞诱导百里香上皮细胞及其在同种异体移植中的应用
- 批准号:
15H04915 - 财政年份:2015
- 资助金额:
$ 39.96万 - 项目类别:
Grant-in-Aid for Scientific Research (B)