A Single Conical Tube Device for Precision CAR-T Cells Manufacturing

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Biospecimen Science Technologies
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Not Applicable
PROJECT SUMMARY/ABSTRACTChimeric-antigen-receptor T cells (CAR T cells) have achieved extraordinary success in treating B cellmalignancies and have demonstrated high potential for treating solid tumors. However, their widespread use islimited by a number of difficulties in manufacturing such cells. Current manufacturing processes are complicated,costly, and can only produce cells for small populations. Additionally, they have large production variations. Asa result, different patients receive very different products or treatments. The long-term goal is to develop a noveltechnology to address the CAR T manufacturing challenge. Toward this goal, the team has developed a proof-of-concept technology termed stress-free intra-tubular cell culture technology (SFIT). SFIT provides cells uniform,highly reproducible, controllable, and cell-friendly microenvironments, resulting in extremely high cultureefficiency and consistency. SFIT produces cells for each patient with one small conical tube, significantlyreducing production cost and increasing production capability. The purpose of this project is to further developand validate this technology and the associated methods to make it ready for the final translational challenge.Leveraging sound preliminary studies and a diverse team of experts, the specific aims are to (1) validate SFITfor culturing T cells from a wide range of donors and for culturing various T cell subtypes, (2) further develop andvalidate methods for transducing T cells with lentivirus and ?-retrovirus in SFIT, and (3) further develop andvalidate the SFIT-based single-conical-tube-device for producing autologous CAR T cells. The project will buildon the team?s strong preliminary work and include mathematical modeling, prototype device design, extensive Tcell culturing, exome-Seq and RNA-Seq data analyses, in vivo testing, statistical analyses and comparisons, andpartnership with ADS BIOTEC, a company that designs, builds, and sells instruments for processing human cells.With the completion of this project, simple, disposable, affordable devices for the scalable, cost-effective andconsistent production of autologous CAR T cells are expected. This technology can also be scaled up forproducing allogeneic CAR T cells in large scales if needed. This technology will not only make CAR T cellsbroadly accessible, but also make the product much more consistent and predictable. Based on 2012-2014 data,approximately 38.5% of the human population will be diagnosed with some type of cancer during their lifetime.Currently, only about 67% of cancer patients will survive five years after diagnosis. CAR T cell therapy isexpected to significantly increase their chances of survival. The technology developed in this proposal will makeCAR T cells available to many patients.