GPB Scientific, Inc. — Department of Health and Human Services STTR Phase I: 101

Description

ABSTRACT The goal of this Fast Track STTR project is to develop a Deterministic Lateral DisplacementDLDmicrofluidic device that can enrich white blood cellsWBCsfrom a typical leukapheresis unit inhrfor use in manufacturing cancer cellular immunotherapyChimeric antigen receptor T cellCAR Ttherapy has been recommended for FDA approval to treat relapsed or refractory pediatric and young adult patients with B cell acute lymphoblastic leukemiaThere is a critical need for cost effective automated methods to improve the efficiency and yield of large scale enrichment of WBCs for use in manufacturing CAR T and other cellular therapiesGPB is a pioneer in developing novel DLD microchips to process blood cells for cell analysisGPB now proposes to developevaluate and commercialize a compact device in which an entire leukapheresis unitup toxWBCs in up tomlcan be processed in aLeuko stackof disposable single use multi channel DLD chips to produce inhr a washed cell suspension that is enriched in WBCs and depleted of red blood cellsRBCsand plateletsPLTIn Phase IAimis to increase cell throughput through the current prototype chips byoptimizing DLD chip design and operation to increase flow rateincreasing throughput by stacking plastic chips and running them in parallelLeuko stacksandtranslating chip production to high volume manufacturing material such as Cyclic Olefin PolymerCOPFinal Phase I milestones to proceed to Phase II arefinal chip design with a flow rate of at leastmL hr via a single chipat leastrecovery of viable WBCs and immunophenotypedefined T lymphocytesand ability to process cells forhr without cloggingLeuko stack of at leastchips run in parallelwith the same output as incombined increases in throughput viaandsufficient to process aml leukapheresis unit inhrconfirmation that the chips can be produced from COPIn Phase IIAimis to build final prototype COP plastic chip based microfluidic device capable of processing a leukapheresis sample atmL hrAimis to test performance of prototypes from Aimwith leukapheresis aliquots and then full size human leukapheresis samplesThe final milestone of this project is to produce a set of commercial prototype Leuko stacks that can process an entireml leukapheresis unit inhr with at leastWBC and T lymphocyte recoveryat leastdepletion of RBCsat leastdepletion of PLTsand at leastrecovery of T cell expansion capacityas compared with the input samplesin significantly more thanof samples tested atsitesThe GPB Leuko stack platform will preserve the advantages of DLD microfluidic cell processing over current methodswhile massively increasing throughput rate and cell processing capacitythus transitioning from analyticto preparative scale WBC enrichment for subsequent manufacture of CAR T and other cell therapies PROJECT NARRATIVE Targeted cellular immunotherapies for several hematologic malignanciesand potentially for solid cancersare nearly at handIn order to increase their availabilitythere is a critical need for better methods to efficiently and cost effectively isolate large quantities of the white blood cells needed to manufacture the therapeutic cells in sufficient quantitiesThis project proposes to scale up a proprietary microfluidic cell processing technology to enrich white blood cells from leukapheresis harveststhe first step in engineering manufacture of therapeutic chimeric antigen receptor T cellsCAR Tthat can cure leukemias and other cancersSuccessful completion of this work will result in a well characterized prototype for a white blood cell enrichment device that will be ready for product development and extensive testing and suitable to meet regulatory approval standards