SBIR-STTR Award

Vanquish Bio is an immunotherapy company reimagining treatment of cancer with the use of unique naturalkiller (NK) cell derived extracellular vesicles (EVs). The goal of this STTR is to develop a therapy using naturalproducts 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 theU.S. in 2019. Despite treatments that include stem cell transplantation and/or chemotherapy, patientsinevitably relapse. New innovations are needed that extend survival, increase durability of remission andprovide options to patients ineligible for front-line therapy. We developed NK3.3, a human NK cell line derivedfrom a healthy donor. These cells kill an array of tumor types. Using a minimal residual disease mouse modelof human MM, administration of NK3.3 EVs prevented tumor recurrence for up to 100 days, versus 21 dayswithout treatment. As NK3.3 grow in culture, they release EVs as small membrane-bound structures that arealso capable of killing many different tumor cells without harming normal cells. NK3.3 EVs also kill cancer stemcells (CSC); these are resistant to standard chemotherapy and responsible for metastasis and recurrence. NKEVs can be produced in large quantities, frozen, stored and then thawed, without loss of function. Otheradvantages of using NK3.3 EVs include: 1) resistance to the hypoxic tumor microenvironment, 2) ability tocross the blood-brain barrier, 3) stability and 4) low toxicity. EVs are not restricted by blood group orhistocompatibility and are therefore an immunotherapeutic modality that can be a universal treatment. Our goalis to develop a new infusion therapy product that will improve survival rates with less side effects for MMpatients with relapsed/refractory or stable disease.Phase I is to generate NK3.3-derived EVs and demonstrate efficacy against MM and extend durability ofremission, with minimal, toxic side effects.Specific Aim 1: Identify activators that maximize tumor killing activity of NK3.3 EVs. NK EVs will beisolated from NK3.3 cells cultured with activating cytokines IL-2, IL-12 and IL-15 individually and incombinations. Our goal is to prepare NK EVs that kill ≥90% of tumor cells within 72 hours of treatment, withless than 10% normal cell death.Specific Aim 2: Determine proof-of-concept efficacy with low toxicity of NK EVs in MM-bearingimmunodeficient mice. We will administer different concentrations of NK EVs in MM-bearing immunodeficientmice with stable disease. The goal is to extend remission beyond 21 days in ≥50% of mice. Toxicity will bemeasured for qualitative visible signs and behavior, and quantitative variation in body weight, organ weight andblood chemistry. We will prove feasibility of producing more potent NK EV preparations with anti-MM activityand proof-of-concept oriented efficacy and toxicity data of NK EV therapy against MM.

Public Health Relevance Statement:
New innovations are needed that extend survival and increase durability of remission for myeloma patients. We developed a natural killer (NK) cell line, NK3.3, that releases small membrane-bound nanoparticles (EVs) with strong tumor killing activity, while sparing normal cells. The goal of this STTR project is to establish the feasibility of producing potent NK EV preparations with anti-tumor activity and low toxicity, as a first step towards generating preclinical data for future clinical studies.

Project Terms: