QC and Release Testing of Clinical Vector and Cell Gene Therapy Products

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

The SBQC team executes multiple assays to demonstrate conformance of viral and cell products manufactured both at the Surgery Branch and from external labs such as Contract Manufacturing Organizations (CMOs). All assays are executed according to specific GMP compliant SOPs and the specifications for product use are captured on the Certificate of Analysis (COA). These assays are complex cell-based, multi-day assays that are executed under time constraints to meet clinical patient treatment schedules - as each product (virus or cell) is unique and intended for a single, unique patient. Both the vector (encoding a patient specific TCR targeting a mutant neoantigen) and the cells transduced with this vector must conform to the COA specifications. Release of Vector: The assays required to demonstrate that a vector produced at the SB or other facility is appropriate, safe and meets specification for clinical use are: vector titer, TCR specificity and presence (absence) of replication competent retrovirus, residual plasmid, residual benzonase endonuclease and sterility (microbiology, endotoxin and mycoplasma). All assays except the sterility assays are performed by the SBQC group. Release of Cell Products: The assays required to demonstrate that cellular products manufactured at the SB is appropriate, safe and meets specification for clinical use are: transduction efficiency, TCR specificity, presence (absence) of replication competent retrovirus, residual plasmid, residual benzonase endonuclease, vector copy number (per cell) and sterility (microbiology, endotoxin and mycoplasma). All assays except the sterility assays are performed by the SBQC group. The SBQC unit since its inception in 2018 has performed testing on 70 individual vector products and 40 individual cellular products. An unfortunate consequence of personalized therapies with long lead times from discovery of patient specific TCRs through to a vetted patient treatment is that many vector products are made but not used as the patient becomes ineligible due to disease progression before the treatment is ready. This is the primary cause for the discrepancy in vectors tested for clinical use versus patient products generated for treatment/infusion. Other unique factors of the trials supported by this project are that some vectors are made for allogeneic use (TCR identified in another patient, but vector used in manufacturing of patient autologous cells for treatment) as well as some TCRs are transferred to clinical vector production but the data generated by the research team is either incomplete or cannot be replicated using the GMP-qualified assays.