Development and Optimization of a GMP-Compliant Manufacturing Process for a Personalized Tumor Lysate Dendritic Cell Vaccine.

Details

Serval ID
serval:BIB_8FCD2C6F2CCA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Development and Optimization of a GMP-Compliant Manufacturing Process for a Personalized Tumor Lysate Dendritic Cell Vaccine.
Journal
Vaccines
Author(s)
Boudousquié C., Boand V., Lingre E., Dutoit L., Balint K., Danilo M., Harari A., Gannon P.O., Kandalaft L.E.
ISSN
2076-393X (Print)
ISSN-L
2076-393X
Publication state
Published
Issued date
14/01/2020
Peer-reviewed
Oui
Volume
8
Number
1
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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.
Keywords
GMP, dendritic cell, immunotherapy, manufacturing, tumor lysate, vaccine
Pubmed
Open Access
Yes
Create date
23/01/2020 16:45
Last modification date
26/08/2020 6:26
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