Lymphocytes, expanded for clinical use, often consist of a small selected starting population, which requires multiple rounds of replication to achieve therapeutic doses. By using perfusion culture with the WAVE Bioreactor 2/10 System, high cell density cultures which are sufficient for therapeutic doses, can be generated. The Cellbagâ„¢ bioreactors, used together with the WAVE system, are functionally closed, single-use bioreactors that are delivered pre-sterilized and suitable for cGMP production. Perfusion is automatically maintained by the WAVE system, which removes metabolites through an internal filter while supplying the culture with nutrients.1

The handling of only one culture using the WAVE system, compared to having to manipulate multiple T-flasks or static bag cultures, simplifies the handling and sampling process. Samples can be withdrawn from the Cellbag Bioreactor through the sample clave port, by connecting e.g. a Luer syringe, thus keeping the system functionally closed. Cells produced for use in clinical trials often need to meet specific release criteria, which can include showing that the product contains low levels of endotoxin and is sterile.

Rolf Kiessling and his team are currently running a phase I clinical trial to evaluate safety, feasibility and immunologic response of adoptive T cell transfer with or without dendritic cell vaccination in patients with metastatic melanoma (ClinicalTrials.gov identifier: NCT01946373). A protocol for in vitro expansion of tumor infiltrating lymphocytes (TILs) using the WAVE 2/10 system has been developed and cells expanded with this protocol have been shown to meet the release criteria defined in the clinical trial and can be used for adoptive T cell transfer.