With the 25th anniversary of the Belfer Gene Therapy Core Facility approaching next year, Dr. Stephen Kaminsky, professor of research in genetic medicine and associate director of the facility, shared with us the history and successes of this cutting-edge research facility. It has played a vital role in supporting Cornell University, the National Institutes of Health (NIH) and other U.S. and international investigators in constructing, producing and testing clinical gene therapy vectors.
Dr. Kaminsky, you helped build the Belfer Gene Therapy Core Facility. How did you become interested in designing facilities and in gene therapy?
My undergraduate training in engineering physics at Cornell provided the conceptual basis of facility design and specifications. After working in laboratories at several industry and academic institutions, I realized that I had an interest in designing and outfitting a facility.
My background included heading manufacturing of active ingredients for licensed products, as well as, designing clinical trial candidates at a biotech company. We conducted about six or seven clinical trials for HIV vaccines and therapeutics, diagnostics for various infectious agents and therapeutics for prostate cancer.
When Dr. Ron Crystal, the chair and professor of genetic medicine, received funding for the Belfer facility from the college and the NIH, it was a perfect match—he was looking for somebody who had the design skills but didn’t have experience in gene therapy because he wanted to gain unbiased insights into gene therapy at the time. Our team included a variety of people with expertise in different scientific disciplines that weren’t necessarily gene therapy. I also had the opportunity to work with a wonderful colleague, Lou Kennedy, Capital Projects director, at Weill Cornell Medicine.
I worked with consultants and the architect to lay out the GMP (Good Manufacturing Practices) manufacturing facility and the basic research and animal facilities. I also designed and picked out which equipment to buy. Once the facility was built, we had to carry out a set of qualification protocols.
Over the years, we grew into a much larger group for the manufacturing side. With the increasingly stringent requirements from the FDA, we gradually built up a staff of GMP-trained technicians. We now have six to seven technicians, and two quality assurance staff. In addition, we have a GMP manager and an overall quality manufacturing assistant director. To further my interest, I've consulted on the designs of other facilities outside Weill Cornell Medicine throughout my career.
Dr. Stephen Kaminsky (Provided)
What services does the Belfer Gene Therapy Core Facility provide to our investigators? Who has access to its services?
We basically provide two different services in the core facility. First, investigators can pay monthly to learn the process for the construction and production of viral vectors, as well as characterization and quality testing of vectors at our labs. After they master the technology, investigators can produce the vectors they need in their own labs and be in control of turnaround time, as opposed to depending on a third party. This enables other Cornell researchers to independently develop and acquire funding for their own research programs.
Our GMP facility also manufactures clinical grade and toxicology grade drug products, such as adeno-associated viruses (AAVs), for clinical trials and safety and toxicology studies for investigators within the Cornell University ecosystem. We have supported outside clients, such as biotech companies, the NIH and other academic researchers. We have been around for a long time and developed a strong reputation. Therefore, we have both domestic and international clients, including foundations in Italy and Australia, and academic institutions in England and France.
Of course, we also support our own Weill Cornell Medicine basic research ideas or projects that have a potential pathway to clinical trials. We'll help move products forward that are successful in their basic research lab to safety and toxicology studies in our animal facility. Once complete, the data is provided to the FDA, and when allowed, we move on to manufacturing vectors that are used in clinical trials.
We've conducted homegrown clinical trials for drug concepts targeting a range of therapeutic areas from Alzheimer's disease to angiogenesis (improving vascularity of the heart) and treatments for drug addiction and several rare diseases.
Finally, we provide guidance ad hoc to faculty at Weill Cornell Medicine on the use of viral vectors. Academic researchers without experience in the steps required to take a project from the lab to the clinic will turn to us. We inform them about all the things critical for getting into the clinic, such as drug development, stability studies and device compatibility studies, etc.
We hold their hands through the whole process, teaching them what is required for the basic proof-of-concept studies, safety and toxicology studies and regulatory submissions.
If they make a clinical vector with us, we then write a significant portion of their FDA submission related to the manufacture of the drug product. In support of Cornell derived inventions, I've drafted technology disclosures as well as proofread patent applications and developed the template master services agreement with Cornell counsel.
Can you tell us about some memorable projects you participated in? Were any of the drug targets licensed or commercialized? What role did you play in helping the principal investigators?
I've been involved in virtually all the basic research that has moved out of the lab here to the clinic. It's been fun and adventurous. The ultimate goal and motivation are to help patients improve their health and quality of life.
Our first totally homegrown clinical trial was for Batten disease, also called CLN2 disease—a rare, fatal inherited genetic disorder that affects the brain and nervous system. We conducted the first clinical trials of AAV in early 2000s with Dr. Mark Souweidane, a professor of neurological surgery in pediatrics at Weill Cornell Medicine. We administered the gene therapy into 12 distinct cerebral locations in the brain of affected children. We took this idea from the bench into a clinical trial in four years, which is pretty much unheard of. Together—Dr. Crystal and my colleagues in Genetic Medicine, Drs. Dolan Sondhi and Neil Hackett as well as a large team at the Gene Therapy Core Facility—we led the basic research, safety studies, drug manufacture and regulatory submissions.
It was the first time I took part in a neurosurgery running the pump that delivered the drug into the brain of the child. We manufactured the catheter ourselves and demonstrated that it was efficacious and compatible with the drug as a delivery method.
Currently, our Alzheimer's project has the potential to impact the largest number of people among our projects, it appears to be safe and there are hints of efficacy. Seven participants in the clinical trial were treated here at NewYork-Presbyterian/Weill Cornell Medical Center. We're also working on a second-generation approach in-house that seems even more promising. The target is now fully licensed to LEXEO Therapeutics, which went public last year and was co-founded by Dr. Ron Crystal.
Additionally, we have a gene therapy trial for cardiomyopathy due to Friedreich’s Ataxia (FA), an inherited progressive, incurable disease that affects the heart and nervous system. I'm a co-PI on the grant. We also have a clinical trial for a vaccine that we developed to treat cocaine addiction, with another to treat fentanyl overdose in development.
We've constructed and produced a protein production cell line for Dr. John Moore, professor of microbiology and immunology, who is developing an HIV vaccine with his research team. Then, it was transferred to a larger company to grow the cells and produce the protein in large scale.
XylorCor is another company based on Dr. Crystal’s work that licensed a product for the treatment of diffuse coronary artery disease. I was involved in the early studies. They're now in late Phase II clinical trials.
The core facility actively reaches out to Ithaca-based faculty for other collaborations. Ultimately, it’s a clinical trial that tells you whether your idea will work or not. We’re an enabling resource in the sense that we allow investigators to develop ideas in their labs and approach funding agencies with the capacity to bring their proposals for clinical trials to fruition with access to our clinical drug manufacturing. This provides Cornell University with a translational medicine program to develop and efficiently push forward inventive ideas.