Ultra-low shipping temperatures for cell therapies

Abstract

Background & Aim Cell therapies require a cold chain delivery as part of the production and delivery process. Whether following an autologous or allogeneic route, a common workflow for manufacturing cell therapies consists of collecting a cell sample from a healthy donor or a patient, cryopreserving and shipping it to a manufacturing site for engineering purposes, cryopreserving the resulting therapeutic product and shipping it to a clinical site for thaw and patient administration. Cryopreservation enables extended shelf-life of cell products and facilitates the logistics. Cryogenic shipping has typically been undertaken using a dry shipper, a vessel containing some liquid nitrogen (LN2) to ensure that the product being shipped remains below approximately -150°C. The precise limits for safe transportation are however poorly understood, with variations methods and temperatures reported, between transport in liquid nitrogen (-196°C), to transport on dry ice (-80°C). This study examined the impact of transferring samples from stable ultra-low temperatures and storing for 5 and 10 days at -120°C, -100°C, -80°C, and -60°C before transfer back to ultra-low temperature storage to mimic the effect of shipping at lower temperatures. Methods, Results & Conclusion Two common cell lines were tested, Jurkats (immortalized human t cell line), and HepG2s (hepatocarcinoma). It was found that while -120°C transfer has no impact on post-thaw outcome, temporary storage temperatures above -120°C resulted in reduced post-thaw function and viable cell number. The reduction in post-thaw outcome was lower after 10 days’ storage compared with 5 days’ storage at all temperatures >-120°C, with the higher the temperature the greater the reduction in post-thaw function and viable cell number. For the transport of cellular therapies, we conclude that the temperature must be maintained at or below -120°C for optimal post-thaw outcome when cryopreserving with a DMSO based cryoprotectant.