Trailhead Biosystems Inc — Department of Health and Human Services SBIR Phase I: 400

Description

Generation of serum free media for expansion of human T lymphocytes and CDHSCs using High Dimensional Design of ExperimentsHD DoEABSTRACT Serum containing mediawhich has a number of poorly defined components with varying concentrationshampers standardization of lymphocyte and hematopoietic stem cell culturesSerum supplements available in the market such as Human Platelet LysateHPLis not a solutionas their composition remains highly variable with a mix of growth factorsmiRNAsmicrovesiclesexosomes and thus difficult to standardize due to significant batch to batch variationAlthough clinical trials are ongoing with T cells expanded in commercially available serum free mediathey are obliged to be supplemented with human Type AB serum to facilitate optimal growth and T cell activationBy using Trailhead BiosystemsandaposQbD approach on primary human bone marrow isolates and a novel clustering algorithm developed by the companywe previously mapped the fate space of early hematopoiesis and identified completely novel set of input factors related to long term marrow populating cellsLT HSCGiven the importance of advanced cell culture systems for successful manufacturing of T cells and HSCs therapiesthis project further aims to determine optimal conditionsmost effective effector combinations and concentrationsto develop serum freechemically defined media formulations by using highdimensional DoE designs for pathway interrogation along with Multivariate Data AnalysisMVDAThese novel media will be validated for their proliferative response on activationphenotypeand functionality comparatively against serum substituted media andserum alternativecommercially available mediaThis project will deliver two optimized media formulationsT SFMOPT and HSCSFMOPT each specific to serum free expansion of T cell and HSCsrespectivelyThe commercial and clinical impact of the project rests on improved and successful clinical outcomes of transplanted T cells and LT HSCs expanded in serum free media for treating life threatening hematological and immunological diseases PROJECT NARRATIVE For standardization of cells used in research and to improve safetyefficacy and minimize batchbatch variability in cell manufacturing of T cell and HSC therapieswe propose to use Trailhead Biosystems Quality by DesignQbDplatform to develop industrial gradechemically definedserum free optimized cell culture media T SFMOPT and HSC SFMOPT each specific to the expansion of T cells and LT HSCs respectivelyOptimized media will be validated for their activationproliferationphenotype and functionality with a licensing for manufacture endpointExpected clinical outcomes relate to significant superiority in all aspects of cell manufacturing compared to current SFM and serum alternative mediaThe T SFMOPT impacts the current problems encountered in CAR T cell areaHSC SFMOPT product will positively impact bone marrow transplants clinically