Bioactive Surface Engineering for High Yield Manufacturing of Dendritic Cell-Based Cancer Therapeutics

PROJECT SUMMARY Dendritic cellsDCare antigen presenting cells that identify and capture foreign bodies and play an essential role in activating both the adaptive and humoral immune responseDCs are an attractive vehicle for therapeutic manipulationparticularly in cancerand are used in antigen pulsed autologous DC therapies and DC stimulated autologous T cell therapiesHoweverdirect isolation of patient specific DCs is challenging since they are present in very low concentrationsandltin human blood and their ex vivo generation using monocytes or stem cell precursors using the industry standard manual culture is time consuminglaborintensive and subject to user variabilityThe manual technique remains the standard even in clinical manufacturinge gfor the first DC vaccine Provengewhich currently treats aroundpatients per year in the USbecause no effective system exists for automated dendritic cell generation in a single usepatientspecific formatYeta significant market exists for such automated systemsThere are andgtclinical trials currently ongoing clinical trials in newprecisely targeted dendritic cell vaccines and T cell therapies produced using patient specific and tumor specific neoantigen stimulated DCsTo meet this significant clinical and market needFlaskworks is developing a suite of proprietary automated systemsincluding MicroDENa perfusion based automated culture system for patient specific DC generationIn its current formthe MicroDEN cell culture cartridges consist of untreated polystyrene which has limited capacity to adhere monocytesIn this proposalwe describe an approach to engineer the surface of the MicroDEN cartridges to significantly increase monocyte adhesion and thereby DC yielda crucial attribute for clinical manufacturingMicroDEN Plus cartridges will be designed by mimicking key aspects of the in vivo environmentincluding presentation of ECM signals to enhance monocyte adhesion and drive their conversion to DCsGiven that no automatedsingle use system of this kind is currently availablewe expect the MicroDEN Plus system to have significant impact in the manufacturing of DCs for clinical use in DC vaccines and DC stimulated T cell therapies PROJECT NARRATIVE Dendritic cells are responsible for the body s response to disease and infection and in the next generation of cancer therapy these cells are generated from a patient s white blood cells and modified to target specific tumorsThis project will develop new technology to manufacture dendritic cells in a cost effective manner