RESEARCH SUMMARY

Dr. Beyer is the head of the NCI Surgery Branch Vector Production Facility (VPF) and in addition, heads the Quality Control Unit (QCU) for clinical products used within the Branch.  In these roles, Dr. Beyer directs a GMP viral vector pipeline for individualized therapies including manufacturing and testing/release of clinical vectors and testing/release of gene therapy cell products. Dr. Beyer is also responsible for identification and development of novel strategies to improve gene delivery in support of Surgery Branch priorities.  Dr. Beyer provides support IND applications/modification and facilitates CRADA partnerships with industry in a leadership role.    

Dr. Beyer leads a program to develop and train staff on novel SOPs required to manufacture γ-retroviral vectors encoding T-cell receptors (TCRs) targeting unique neoantigens in patients in a cGMP compliant manner.  Previous work in the Surgery Branch and across the industry focused on methods for large scale production and testing to treat many patients using the same vector with timelines just for vector production/testing approaching 12 months.  Developing small-scale platforms that meet FDA approval for both manufacturing and testing and also meet Surgery Branch requirements for compressed timelines that are relevant for patients refractory to frontline therapies was a significant challenge.  Specifically, Dr. Beyer developed and qualified for FDA/cGMP acceptance a small-scale (single patient) production strategy and all required in-house Quality Control (QC) assays (sterility is outsourced to another laboratory):  FACS assay to determine functional viral titer, co-culture assay with effector cells and target APCs, ELISAs to quantify IFNγ release and residual benzonase endonuclease, qPCR assays to quantify integrated copies, residual plasmid and (absence of) replication competent retrovirus.  Dr. Beyer also developed a pipeline to expand B cells (a relatively ‘renewable’ resource) to quantities appropriate for several levels of plasmid-encoded TCR quality control testing (plasmid, vector production, cell production) given the limited quantities of monocytes/dendritic cells in peripheral blood mononuclear cells.  From the time plasmids encoding the individualized TCR(s) are available to a viral vector supernatant that has met all FDA sanctioned Certificate of Analysis (COA) specifications for clinical use, Dr. Beyer’s in-house pipeline requires less than 6 weeks.  This achievement is a key component that enables the Surgery Branch to pursue individualized therapies that use viral vectors for gene therapy.

The VPF and QCU team members provide expert technical support to ensure clinical priorities and timelines are met in a GMP compliant manner.  

Areas of Expertise

1) Adoptive Cell Therapy

2) Virology/Viral Vector Production (RVV, LVV, adeno- and adeno-associated)

3) Gene Therapy

4) Immunotherapy

5) GMP and Regulatory Requirements (21 CFR Part 11/210/211)

6) IND/CMC creation/submissions