Clinical scale rapid expansion of lymphocytes for adoptive cell transfer therapy in the WAVE® bioreactor

Robert Pt Somerville,Mark E Dudley,Steven A Rosenberg,Maria R Parkhurst,Laura Devillier

doi:10.1186/1479-5876-10-69

Robert Pt Somerville, Mark E Dudley + Show 3 more

Open Access

https://doi.org/10.1186/1479-5876-10-69

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Abstract

BackgroundTo simplify clinical scale lymphocyte expansions, we investigated the use of the WAVE®, a closed system bioreactor that utilizes active perfusion to generate high cell numbers in minimal volumes.MethodsWe have developed an optimized rapid expansion protocol for the WAVE bioreactor that produces clinically relevant numbers of cells for our adoptive cell transfer clinical protocols.ResultsTIL and genetically modified PBL were rapidly expanded to clinically relevant scales in both static bags and the WAVE bioreactor. Both bioreactors produced comparable numbers of cells; however the cultures generated in the WAVE bioreactor had a higher percentage of CD4+ cells and had a less activated phenotype.ConclusionsThe WAVE bioreactor simplifies the process of rapidly expanding tumor reactive lymphocytes under GMP conditions, and provides an alternate approach to cell generation for ACT protocols.

Highlights

To simplify clinical scale lymphocyte expansions, we investigated the use of the WAVE®, a closed system bioreactor that utilizes active perfusion to generate high cell numbers in minimal volumes
In this paper we investigate the use of the WAVE bioreactor, a system that utilizes continuous media exchange, to rapidly expand tumor infiltrating lymphocytes and genetically modified PBL under GMP conditions for clinical trials
Active perfusion of the WAVE bioreactor creates A stable culture environment We wanted to determine if the culture environment of lymphocytes rapidly expanded in the WAVE bioreactor, with its active perfusion of media, was more stable than that of lymphocytes undergoing rapid expansion in static bags with an episodic feeding regimen

Summary

Introduction

To simplify clinical scale lymphocyte expansions, we investigated the use of the WAVE®, a closed system bioreactor that utilizes active perfusion to generate high cell numbers in minimal volumes. The FDA currently approves three treatments for metastatic melanoma, dacarbazine [2]), interleukin-2 [3], and ipilimumab [4]. Dacarbazine has an objective response rate of 10-15% with few, if any, durable remissions [2]. IL-2 has an objective response rate of about 15%, with a complete response of less than 5% [2,5]. In a large randomized trial with ipilimumab, the objective response rate was reported to be about 10%, with 0.6% complete responses [4]. Inhibitors of dominant BRAF mutations are currently in large, randomized clinical trials, and could be approved in the near future [6]. Phase II studies with these agents did not result in a durable complete response for most patients and so additional approaches to treating advanced melanoma are required

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