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TCR-engineered T cells and CAR T cell manufacturing on clinical scale

Engineered T cells for cancer therapy and other therapeutical applications

Chimeric antigen receptor (CAR) T cell therapy is undoubtedly leading a revolution in cancer therapy.1 Recent successes in treating hematologic malignancies with CAR T cell therapy and the availability of several commercial products have prompted increased interest in cancer immunotherapy.2 These advances have also opened new lines of research looking to optimize the safety and efficacy of CAR T cell therapies via complex gene engineering3 and promising developments like engineered T cell receptors (TCRs).4 More recently, genetically engineered T cells are also being applied in other indication areas like solid tumors, infectious diseases, and autoimmunity.5-7 

Overview of the CliniMACS Prodigy T Cell Transduction (TCT; above) and CliniMACS Prodigy T Cell Transduction – Large-Scale (TCT-LS; below) used in CAR T cell and TCR-engineered T cell manufacturing.

TCR-engineered T cells and CAR T cell manufacturing on the CliniMACS Prodigy®

Currently, CAR T cell and TCR T cell production consists of various complex process steps. GMP cell manufacturing is labor intensive, and as such, represents a significant challenge in further development of gene-modified T cell therapies.  The CliniMACS Prodigy T Cell Transduction (TCT) and CliniMACS Prodigy T Cell Transduction – Large-Scale (TCT-LS) provide a unique all-in-one solution to this challenge. Well-established and widely used in clinical settings8–12, the CliniMACS Prodigy Platform generates gene-modified T cells via viral transduction in a standardized and automated process.13 The closed system is a breakthrough in cell manufacturing designed to facilitate the transition of novel strategies like TCR T cell therapies to clinical use.4

Overview of the CliniMACS Prodigy T Cell Engineering (TCE) used in complex engineered T cell manufacturing.

Non-viral T cell engineering on the CliniMACS Prodigy

The CliniMACS® Electroporator expands the cell processing capabilities of the CliniMACS Prodigy Platform to include non-viral gene-engineering in a closed and automated fashion. Electroporation parameters are flexibly adaptable to optimize transfection protocols for different gene-engineering technologies, such as TALENs, CRISPR/Cas, zinc finger nucleases, the Sleeping Beauty transposon system, siRNA, and more. The CliniMACS Prodigy T Cell Engineering (TCE) enables complex T cell engineering via electroporation and/or viral transduction, leading the way in GMP-compliant gene engineering.14–16

An overview of gene-engineered T cell manufacturing options with the CliniMACS Prodigy Platform

 CliniMACS Prodigy T Cell Transduction (TCT)CliniMACS Prodigy T Cell Transduction Large-Scale (TCT-LS)CliniMACS Prodigy T Cell Engineering (TCE)
Main applicationCAR T cell manufacturingTCR T cell manufacturingComplex engineered T Cell manufacturing
General featuresT cell isolation, activation, viral transduction, expansion, rebuffering, and harvestT cell isolation, activation, viral transduction, expansion, rebuffering, and harvestT cell isolation, activation, viral transduction and/or electroporation, expansion, rebuffering, and harvest
Starting materialHeterogenous blood products like whole blood, buffy coat, leukapheresisFresh or frozen leukapheresisHeterogenous blood products like whole blood, buffy coat, leukapheresis
Gene engineering methodViral transduction (lentivirus or retrovirus)Viral transduction (lentivirus or retrovirus)Electroporation and/or viral transduction (lentivirus or retrovirus)
Culture capacity (volume)250 mL600 mL250 mL
Number of harvested T cells~5x109~2x1010Electroporation included: ~2x109
No electroporation: ~5x109