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,利用独特的天然成分重新构想癌症治疗
项目成果
期刊论文数量(0)
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JACKI KORNBLUTH其他文献
JACKI KORNBLUTH的其他文献
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{{ 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:
8243104 - 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:
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:
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