Development of a robotic cluster for automated and scalable cell therapy manufacturing

Abstract

The production of commercial autologous cell therapies such as chimeric antigen receptor T cells requires complex manual manufacturing processes. Skilled labor costs and challenges in manufacturing scale-out have contributed to high prices for these products. Here, we present a robotic system that uses industry-standard cell therapy manufacturing equipment to automate the steps involved in cell therapy manufacturing. The robotic cluster consists of a robotic arm and customized modules, allowing the robot to manipulate a variety of standard cell therapy instruments and materials such as incubators, bioreactors, and reagent bags. This system enables existing manual manufacturing processes to be rapidly adapted to robotic manufacturing, without having to adopt a completely new technology platform. Proof-of-concept for the robotic cluster expansion module was demonstrated by activating and expanding human CD8+ T cells. The robotic cultures showed comparable cell yields, viability, and identity to those manually performed. Such modular robotic solutions may support scale-up and scale-out of cell therapies that are developed using classical manual methods in academic laboratories and biotechnology companies.

Competing Interest Statement

Brigitte Schmittlein, Alexis L. Jones, Yasmine Ainane, Ali Rizvi, Darius Chan, Elaine Dickey, Kelsey Pool Kenny Harsono, Dorothy Szymkiewicz, Umberto Scarfogliero, Varun Bhatia, Amlesh Sivanantham, Nadia Kreciglowa, Allison Hunter, Miguel Gomez, Adrian Tanner wish to disclose that they are current employees of Multiply Labs, Inc. or were employed with the company at the time of this study execution. They hold equity in the company. Alice Melocchi and Federico Parietti wish to disclose that they are co-founders of Multiply Labs, Inc. and hold the position of Chief Scientific Officer and Chief Executive Officer, respectively. Sabrina Carmichael wishes to disclose that she is employed by Cytiva, which is a company active in the cell therapy manufacturing space. Holger Aulbach and Xavier De Mollerat Du Jeu wish to disclose that they are employed by Thermo Fisher Scientific, which is a company active in the cell therapy manufacturing space. Matthew Hewitt wishes to disclose that he is employed by Charles River Laboratories, which is a company active in the cell therapy manufacturing space. Benedetta di Robilant is a paid advisor to Multiply Labs, Inc. and holds equity in the company. Jonathan H. Esenstenb is a paid advisor to and receives sponsored research funding from Multiply Labs, Inc. He serves on its scientific advisory board, and holds equity in the company. He receives sponsored research funding from Lonza, Inc. for the development of cellular therapy manufacturing devices.