Stimuli-responsive reagents for improved cell isolations and activations

DESCRIPTION provided by applicant Chimeric antigen receptor CAR T cell adoptive immunotherapy has shown great promise in clinical trials for the treatment of cancers including acute lymphoblastic and chronic lymphocytic leukemia CAR T cell therapies are comprised of the patients own T cells autologous T cells that have been genetically engineered to express a CAR This receptor is comprised of an extracellular tumor targeted binding moiety fused to intracellular domains with activation and signaling functionalities Unfortunately CART therapy has a complex multi step manufacturing process and no standardized approach has been implemented among various institutions running the clinical trials An efficient cost effective an standardized manufacturing process is critical to the broad application and ultimate success of CART therapy The goal of this project is to develop stimuli responsive reagent systems SRRS for cell isolations and activations that will help to streamline and improve the manufacturing process of adoptive cellular therapies like CAR T cell therapy Magnetic beads are used to isolate and activate T cells in CAR T cell manufacturing These beads have surface bound antibodies and they are either micro Dynal r or nano Miltenyi Biotec sized Neither technology has been adopted universally in CAR T cell manufacturing processes because each approach has shortcomings Nexgeniaandapos s magnetic nanoparticle mNP technology is designed to combine the favorable attributes of microbeads rapid magnetic separation and nanoparticles rapid target binding with the additional benefit of simple nanoparticle removal after cell manipulations The key to achieving this ideal combination is the unique stimuli responsive nature of the Nexgenia mNP These mNP bear stimuli responsive polymers and they change from hydrophilic monodispersed nm diameter particles to micron sized aggregates in response to an environmental stimulus like a temperature change Nexgeniaandapos s SRRS comprise mNP and antibodies conjugated to similar stimuli responsive polymers At low temperatures polymer antibody conjugates rapidly bind cell surface antigens At higher temperatures the polymer antibody conjugates aggregate with the mNP facilitating rapid magnetic isolation of target cells or cell activation To achieve the projectandapos s goal Nexgenia will develop a SRSS with a temperature response of C The SRRS will be used to demonstrate the feasibility of isolating T cells from human peripheral blood mononuclear cells and its performance will be benchmarked against Dynal r CD beads The SRRS will then be used to activate T cells thereby mediating their expansion in vitro A SRRS that isolates and then activates T cells can be readily integrated into cell therapy manufacturing processes and lead to more consistent and better characterized therapeutics An improved CAR T cell manufacturing process would help to realize the clinical and commercial success of adoptive cell therapies and ultimately expand patient access to these promising therapeutics Nexgeniaandapos s SRRS can address this area of great need PUBLIC HEALTH RELEVANCE Nexgenia Project Narrative Adoptive cellular therapies with genetically modified autologous T cells i e chimeric antigen receptor or CAR T cell therapy have shown great promise in clinical trials for cancer although the commercialization of cellular therapies is challenging due to complicated manufacturing processes This project aims to develop a set of reagents to streamline the CAR T cell manufacturing process These reagents will help to provide efficient cost effective and standardized methods that will support broad access to these promising therapeutics for cancer patients