A Novel Perfusion-Based 3D Bioreactor for Effective Selection, Activation, and Transduction of T-Cells for Immuno-Gene Therapy

This application will focus on development of a novel perfusion-based, microbead-free 3D bioreactor to achieve the selection, activation, and gene transduction of T cells in a single continuous processing system.
Categories
Cell and Gene therapies

Industry Need

Current T cell manufacturing methods, adapted from other medical uses, face challenges like high costs, safety concerns, and inefficiencies, especially for leukemia patients. Automation is being developed to address these issues, but its success is still uncertain.

Approach

The proposed solution involves developing a closed-loop perfusion circuit for T cell engineering and expansion using two bioreactors: a small one for selection, activation, and transduction (Stage 1), and a larger one for expansion (Stage 2).

Impacts

The goal of the project is to develop a superior process / platform for selection, activation and lentiviral vector transduction of human T-cells using perfusion bioreactor system

The project will enable continuous processing of T-cells in a closed environment and reduce process costs

Value Statement/Outcomes

By implementing a beads-free, closed-loop T cell manufacturing system, an organization could reduce manufacturing failures and reagent costs by eliminating reliance on magnetic bead platforms, enabling efficient, scalable, and automated ACT production that improves safety and accelerates time-to-market for cell therapies.

Outputs/Deliverables

Demonstration of two different-size bioreactors using 3D printing.

Method to immobilize antibodies to bioreactor surface.

Demonstration of activation of T-cells in the 3D printed single use bioreactor.

Demonstration of bioreactor as a pre-filter for T cell selection and purification.

Demonstration of the perfusion-based beads-free bioreactor has potential to form an automated closed-loop system for cost-effective T cell manufacturing.

Internal Publications

Ling, J., “Technology Today” article, Southwest Research Institute, October 31, 2019.

Presentations

Ling, J. & Milone, M., A Novel Perfusion-based 3D Bioreactor for Effective Selection, Activation, and Transduction of T-cells for Immunogene Therapy, NIIMBL Member Forum, Virtual, April 25, 2019.

Ling, J., A Novel Perfusion-Based Cell Manufacturing Platform for Regenerative Medicinee, RegenMed SA 2019 Annual Conference. San Antonio, TX, February 15, 2019.

Ling, J., A novel scalable manufacturing platform for T-cell activation and expansion in adoptiveT-cell therapy, ECI Advancing Manufacture of Cell and Gene Therapies VI, Coronado, CA, January 15, 2019.

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Project Lead

Southwest Research Institute

Southwest Research Institute

Participating Organizations

University of Pennsylvania