With the emergence of
immune checkpoint inhibitors and adoptive T-cell
therapies, there is a considerable interest in using personalized autologous dendritic cell (DC)
vaccines in combination with T cell-targeting
immunotherapies to potentially maximize the therapeutic impact of DC
vaccines. Here, we describe the development and optimization of a Good Manufacturing Practice (GMP)-compliant manufacturing process based on
tumor lysate as a
tumor antigen source for the production of an oxidized
tumor cell lysate loaded DC (OC-DC)
vaccine. The manufacturing process required one day for lysate preparation and six days for OC-DC
vaccine production.
Tumor lysate production was standardized based on an optimal
tumor digestion protocol and the immunogenicity was improved through oxidation using hypochloric
acid prior to freeze-thaw cycles resulting in the oxidized
tumor cell lysate (OC-L). Next, monocytes were selected using the CliniMACS
prodigy closed system and were placed in culture in cell factories in the presence of
IL-4 and
GM-CSF. Immature DCs were loaded with OC-L and matured using MPLA-IFNγ. After assessing the functionality of the OC-DC cells (IL12p70 secretion and COSTIM assay), the OC-DC
vaccine was cryopreserved in multiple doses for single use. Finally, the stability of the formulated doses was tested and validated. We believe this GMP-compliant DC
vaccine manufacturing process will facilitate access of patients to personalized DC
vaccines, and allow for multi-center clinical trials.