Housed within the Siteman Cancer Center, the Biologic Therapy Core Facility (BTCF) partners with physicians and scientists to manufacture, characterize, and release complex, clinical-grade cell and gene therapy products, imaging agents, and other biologics to support early-phase clinical trials.
The BTCF also supports cellular (e.g. hematopoietic stem cell selections) and tissue therapies (e.g. parathyroid cryopreservation) for Barnes-Jewish Hospital (BJH) patient care. In addition, the BTCF serves as a source of institutional expertise in current Good Manufacturing Practices (cGMP) to investigators across the institution to ensure strict adherence to phase-appropriate cGMP procedures & regulations in order to provide the highest level of drug or biologic, or cellular product quality for clinical trials.
Facility History & Updates
Siteman opened the original facility, located in the Southwest Tower, in 2004, and it was registered with the FDA in 2009. The facility was designed and built to meet the new, and increasingly more stringent, regulatory requirements placed on physician-scientists interested in translating promising pre-clinical research into clinical drugs or agents intended to treat, prevent, or improve outcomes for cancer and other diseases.
The updated facility within the BJC Institute of Health has been fully operational since November 2024. Todd Fehniger, MD, PhD, BTCF Director and Professor in the WashU Medicine Division of Oncology, says the new 7,300 square foot facility was designed with flexibility in mind, due to the varied manufacturing processes and equipment needed for the wide array of cell and gene therapy products, imaging agents, and other drug products utilized within the facility.
“Many academic and industry facilities have dedicated production processes and equipment, and their design is specifically constrained to support only those processes,” says Fehniger. “But in our updated facility, the size and number of suites are based on the type of work we’ve historically supported, with an emphasis placed on being configurable enough to accommodate new programs and their distinct manufacturing processes. It is this flexibility that gives our facility a strategic advantage.”
The new facility also has dedicated cleanrooms to support viral vector production or work with volatile materials. In addition to expanded manufacturing space, there are also new dedicated spaces to support Quality Control and Process Development, in-process and final product release testing, microbiology, materials receipt and storage, housekeeping, and administrative spaces to support operations, manufacturing, and Quality Assurance personnel.
Who is Supported by the Facility?
The BTCF currently works with 56 investigators from 6 departments across WashU. It supports 20 manufacturing programs (58% of them being for cancer research) and 30 clinical trials with 800 subjects enrolled. To date, the facility has supported 477 treatments and/or products for patients at both Barnes-Jewish Hospital and St. Louis Children’s Hospital.
Brian Goetz, BTCF Operations Director, says both ICTS and Siteman funding is critical to success in assisting the transition of early programs into the facility, and to reducing barriers to initiating new cGMP protocols for a variety of diseases.
“This funding supports initial consultations with the facility directors and program leads needed to define program goals, key elements of the manufacturing process, specific equipment needed for production and testing,” says Goetz. “This helps guide program onboarding, establish budgets, and ultimately generate the Manufacturing Production Record (MPR) and ancillary protocols needed to support the investigator’s program.”
Advancements in Research
Three WashU investigators who have seen success in their project being supported by the BTCF are John DiPersio, MD, PhD, Julie O’Neal, PhD and Armin Ghobadi, MD. The investigators’ work with the BTCF has focused on producing and releasing their first CAR-T cell product targeting CS1 for Multiple Myeloma. DiPersio says they believe this cellular therapy may significantly prolong the survival and improve the quality of life for Multiple Myeloma patients whose conventional therapy methods have failed.
“The BTCF has been absolutely critical for our WS CS1 CART project,” says DiPersio. “All of the scale-up and manufacturing required by the FDA for our successful IND application were done with the help of Julie Ritchey in the DiPersio Lab and the outstanding BTCF staff. Currently, the generations of products for the first two patients and 23 additional patients are being manufactured in the BTCF. The advancement of this project would not have been possible without the BTCF.”
The BTCF has also proved to be extremely vital in the research efforts of Cornelius von Morze, PhD. von Morze studies the field of hyperpolarized carbon-13 MRI, a new class of non-radioactive imaging contrast agents that are imaged using MRI. von Morze says that the BTCF has been instrumental in helping to develop tailored protocols for producing the contrast agents and for quality control. von Morze stresses production of these agents for human intent requires compounding steps to be executed in a highly controlled environment, such as the BTCF. The project is currently pending FDA/IND approval.
“The BTCF met our unique project with a ‘can-do’ attitude from the very beginning and engaged with us in a highly collaborative approach to meet our project goals within a quick time frame with very reasonable costs,” says von Morze. “They even provided us with an invaluable lead on our raw material sourcing, which has actually benefitted our entire field. As a junior investigator without previous experience in translational research, there is no way that we could have accomplished this work without the engagement of the BTCF.”
Several other WashU investigators have utilized the BTCF to support their research, as well
- Nupur Ghoshal, MD, PhD, and Eric McDade, DO – production and release of a stable isotope tracer that will be used in a Phase 1b study to assess protein synthesis in participants with mild-to-moderate Alzheimer’s Disease
- Dennis Hallahan, MD – production and release of first clinical-grade monoclonal antibody to demonstrate feasibility of PET imaging in cancer patients with 89Zr-DFO-anti-TIP1
- Todd Fehniger, MD, PhD, Amanda Cashen, MD, and Jeffrey Bednarski, MD, PhD – Natural Killer (NK) Cell Therapy program in relapsed/refractory AML; have made more than 100 NK cell products for patients to date
Ongoing and Future Work
The BTCF continues to work with numerous cell and gene therapy programs for several investigators on the WashU Medicine Campus. The facility also continues to support the production of standard-of-care hemopoietic stem cell products for both Barnes-Jewish Hospital (BJH) and St. Louis Children’s Hospital (SLCH).
Goetz says the facility recently began supporting a new Phase I/II pilot study assessing the ability of memory-like NK cells to consolidate a TCRαβ T cell-depleted haploidentical transplant in high-risk AML. The BTCF will produce and release both the NK cell and TCRαβ T cell-depleted products used in this trial, and these studies will soon extend to engineering memory-like NK cells with CAR.
“The BTCF has several new programs that are just getting underway, and we are seeing current programs expanding in both cancer and non-cancer indications,” says Goetz. “It is truly an exciting time for our facility.”