Please click Additional Files below to see the full abstract

Abu-Absi, Susan

English

Engineering Conferences International

Wednesday, April 26, 2023                                                                     Session 5: CCE for Cell-based Therapies ENGINEERED T-CELL THERAPY: STATE OF THE SCIENCE  Susan Abu-Absi, 2seventy bio susan.abuabsi@2seventybio.com   Key Words: cell therapy, CAR-T, process development  The first chimeric antigen receptor T-cell (CAR-T) products were approved over five years ago.  Since then, significant investment in the field has been made with the goal of bringing additional engineered T-cell products to the market with better efficacy, improved process robustness and reduced costs. Currently approved CAR-T products are autologous, with complex manufacturing processes and challenging supply chains. The first step entails collection of the patient's white blood cells via apheresis. The apheresed starting material is shipped to a cGMP facility for drug product manufacturing, which involves enrichment and activation of T-cells, transduction with a viral vector, and ex vivo cell culture to expand the cells to a target dose of viable T-cells expressing the surface CAR. At the final step of the manufacturing process, the modified cells are formulated and frozen as a drug product, which after testing and disposition, is shipped to the clinical site for infusion into the patient.   Similar to established practices for protein therapeutics, cell therapy processes can be developed and characterized via scale-down models using quality by design principles. Patient-derived cells may not be available in large quantities, so much of process development is conducted using starting material from healthy donors. Demonstration of comparability after process changes and/or manufacturing site transfers is also challenging due to the variability in donor- or patient-derived materials. Although manufacturing and process development present challenges for cell therapies, these autologous products present a tremendous opportunity for understanding critical quality attributes (CQAs), by correlation of drug product attributes with clinical results and via deep cell characterization, e.g., time of flight cytometry (CyTOF).  At 2seventy bio, we have experience developing and launching a CAR-T for multiple myeloma (Abecma®) as well as two cell therapies currently being investigated in clinical trials: a novel dual-targeting, gene edited CAR-T for the treatment of B Cell Non-Hodgkin Lymphoma and a regulatable CAR-T for the treatment of Acute Myeloid Leukemia. This presentation will focus on the science utilized and knowledge gained through these endeavors. In addition, a discussion of current and future cell culture process innovation for enhanced potency and reduced cost of goods and product design to combat the solid tumor microenvironment will be included. There are significant opportunities to apply bioprocessing concepts and expertise to continue to advance cell-based therapies (e.g. allogeneic products, point-of-care manufacturing, in vivo gene delivery), and the CCE community will continue to play a transformational role.   

Engineered T-cell therapy: State of the science

https://dc.engconfintl.org/cgi/viewcontent.cgi?filename=0&article=1039&context=ccexviii&type=additional

Engineered T-cell therapy: State of the science

Abstract

Similar works

Full text

Available Versions

Engineering Conferences International