CellRaft Array for Screening and Isolation of Highly Effective Cytotoxic T Cells

PROJECT SUMMARY
Cell Microsystems Inc is an early stage biotechnology company whose mission is the commercialization
of a novel cost effective platform enabling the identification and efficient isolation of viable cells based on
morphologic and fluorescence signatures as well as characteristics that change over time The CellRaft
technology is based on a unique cell array recently developed by the Allbritton Lab at the University of North
Carolina at Chapel Hill The commercially available CellRaft platform for cell identification and isolation
consists of a sterile disposable microarray the CellRaft Array for culturing cells and a motorized release
device fitting on a standard inverted laboratory microscope for cell isolation
In the current grant application we propose to expand our market applications by developing the
technology for identifying and isolating non adherent immunologic cells based on a unique time resolved
selection criterion a feat not possible with other cell isolation procedures The approach will combine the
CellRaft Array with a cell based cytotoxicity assay to identify and collect antigen specific cytotoxic CD T
lymphocytes CTLs The eventual goal for this project will be to use the platform to isolate highly efficient
killer cells for adoptive cell therapy ACT ACT is an emerging immunotherapy which shows significant
promise in the treatment of both leukemia and solid tumors ACT consists of the isolation and ex vivo
expansion of CTLs recognizing epitopes of a mutated or aberrantly expressed protein present almost
exclusively on the surface of a patient s tumor cells We envision the CellRaft system will serve both as a
research tool enabling correlation of killing efficiency with the molecular characteristics of the T cell receptor
TCR and eventually as a clinical tool for producing and identifying efficacious CTLs for cell based therapies
In this regard we envision the ideal approach to individualize ACT would be to identify enrich and expand a
population of highly efficient CTLs against a patient s tumor without a priori defining a tumor specific antigen
but this feat is not currently possible primarily due to technical limitations To overcome this and other
obstacles we seek to develop a high throughput technology to efficiently generate highly active tumor
directed CTLs In this initial Phase I STTR proposal we will optimize the array for the cell based cytotoxicity
assay improve the protocol for isolating the non adherent lymphocytes and perform feasibility testing by
using the CellRaft technology to identify and isolate effective CTLs These efforts will lay the groundwork for a
follow on Phase II proposal to scale up the array size and integrate automated high throughput image
cytometry and cell isolation procedures to enable the molecular characterization of efficient killer T cells PROJECT NARRATIVE
Adoptive cell therapy ACT is an emerging immunotherapy which shows significant promise in the treatment
of both leukemia and solid tumors ACT consists of the isolation and ex vivo expansion of cytotoxic CD T
lymphocytes CTLs derived from patient samples which immunologically identify and destroy tumor cells
We envision the CellRaft system as both a research tool enabling correlation of CTL tumor cell killing
efficiency and eventually as a clinical tool for producing and identifying efficacious CTLs for cell based
therapies