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

• 批准号: 10383462
• 负责人: JACKI KORNBLUTH
• 金额: $ 39.96万
• 依托单位: VANQUISH BIO LLC
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10383462
• 关键词: ADME Study; Allogenic; Autologous; Behavior; Blood - brain barrier anatomy; Blood Chemical Analysis; Body Weight; Bone Pain; Cell Count; Cell Death; Cell Line; Cell Proliferation; Cell Therapy; Cells; Cessation of life; Characteristics; Chemoresistance; Clinical Research; Clinical effectiveness; Combined Modality Therapy; Control Groups; Data; Development; Diagnosis; Disease; Disease remission; Freezing; Future; Generations; Goals; Growth; Healthcare; Hematologic Neoplasms; Hematopoietic; Histocompatibility; Hospital Referrals; Hour; Human; Immune system; Immunodeficient Mouse; Immunohistochemistry; Immunotherapeutic agent; Immunotherapy; In Vitro; Individual; Infection; Infusion procedures; Interleukin-12; Interleukin-15; Interleukin-2; Kidney; Knowledge; Laboratories; Lead; Managed Care Programs; Measures; Medical Oncologist; Membrane; Metabolic; Modality; Modeling; Multiple Myeloma; Mus; Natural Killer Cells; Natural Products; Neoplasm Metastasis; Normal Cell; Organ; Organ Weight; Outcome; Pain; Particle Size; Patients; Pharmaceutical Preparations; Phase; Preparation; Primary Health Care; Production; Proteins; RNA; Recurrence; Refractory; Refractory Disease; Relapse; Residual Neoplasm; Resistance; Route; Sales; Small Business Technology Transfer Research; Stable Disease; Stem cell transplant; Structure; Survival Rate; Symptoms; Testing; Therapeutic; Tissues; Toxic effect; Variant; blood group; cancer cell; cancer stem cell; cancer therapy; cancer type; cell killing; chemotherapy; cohort; commercial application; cytokine; cytokine release syndrome; experimental group; extracellular vesicles; graft vs host disease; human model; improved; innovation; loss of function; mouse model; nanoparticle; neoplastic cell; patient advocacy group; pre-clinical; prevent; protein expression; side effect; technological innovation; tertiary care; tumor; tumor hypoxia; tumor microenvironment

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