iATMP consisting of monocyte-derived dendritic cells (DC) loaded with mRNA encoding tumor antigens for cancer vaccination.
Manufacturing Process
A 4-day process from monocyte to monocyte-derived DC (moDCs) loaded with mRNA, based on Brabants E. et al. Cytotherapy, 2018. In brief, monocytes are isolated from leukapheresis product using CliniMACS® Plus Instrument. Purified monocytes are then transferred to cell culture bags and cultivated in the presence of GM-CSF and IL-4. At day 3 of cultivation, maturation stimuli are added. At day 4, mature moDCs are harvested and electroporated with mRNA with Bio-Rad Gene Pulser Xcell Electroporation system. Four hours post electroporation, the mRNA-loaded moDCs are frozen at controlled rate with (name of controlled rate freezing machine) and stored in liquid nitrogen.
Quality control tests in place: Sterility, endotoxins, Flow cytometry (identity, purity), mycoplasma, potency
Projects
Midrix-Neo
neoantigen-presenting autologous dendritic cell therapy for NSCLC
Service: Tech transfer, IMPD writing Manufacturing, QC, QP release for phase I clinical trial
Collaborator: Prof. dr. Karim Vermaelen, Prof.dr. Björn Menten, Prof.dr. Francis Impens
completed
Neoantigen-targeted dendritic cell vaccination in lung cancer patients induces long-lived T cells exhibiting the full differentiation spectrum
Ingels J. et al. Cell Reports Medicine 2024
Here, we report the results of a first-in-human clinical trial in which we explored the potential of an autologous DC vaccine targeting neoantigens as adjuvant therapy in early-stage resected NSCLC patients. The primary endpoint of the trial was safety. Secondary endpoints were feasibility, immunogenicity, and relapse-free survival.
An important challenge of Neo-mDC therapy is the extensive coordination required between the different actors and processes (i.e., next-generation sequencing [NGS], immunopeptidomics, bioinformatic analyses, production of the plasmid template, good manufacturing practice [GMP] production of RNA, apheresis of the patient, and finally GMP production of the cell therapy product) in order to streamline the overall production process and time.
In the present trial, fully functional, neoantigen-loaded, monocyte-derived DCs were generated in only 4days, which is associated with reduced costs compared to classical 7/8-day DCs due to fewer operator interventions, less consumables, and less occupation time of ultrapure, class B clean rooms dedicated to aseptic processing.
Further reduction of costs may be achieved by using fully automated, closed cell-culture systems, of which several platforms are currently being developed and actively explored for chimeric antigen receptor (CAR)-T cell production. The introduction of these systems will enable further reduction in operator interventions and reduce the need for class B clean rooms.
Shared cancer antigen presenting autologous dendritic cell therapy for NSCLC
Service: Tech transfer, IMPD writing Manufacturing, QC, QP release for phase I clinical trial
Collaborator: Prof. dr. Karim Vermaelen (UGent/UZGent)
completed
Publication in preparation
Testimonials
The extensive experience and data gathered from this study pave the way for developing even more powerful cell therapies in our center, reinforcing Ghent as a major hub for cell and gene therapies in the region and beyond.
