Supporting Translational Cell Therapy Research

This is the third part of an interview with Renier Brentjens, MD, PhD. For the first part, click here. For the second part, click here. For the third part, click here.

Renier Brentjens, MD, PhD
Credit: Roswell Park

A large amount of nonclinical research has been carried out with regard to chimeric antigen receptor T-cell (CAR-T) therapy technologies. Notably, however, comparatively little of this research has been translated into clinical research.

In an interview with CGTLive®, Renier Brentjens, MD, PhD, the chair of the department of medicine and the deputy director at Roswell Park Comprehensive Cancer Center, brought attention to this issue. He pointed out the prohibitive costs of clinical trials and discussed how the model used at his institution is helping to address this gap.

CGTLive: With regard to CAR-T in oncology, is there anything else you think people in the field should be paying attention to?

Renier Brentjens, MD, PhD: I will say this. If you look right now at the commercially available CARs, the design of the chimeric receptor—those designs were published back, I think, in 2002 and 2004. Since that time, you could stack up all the Science, Nature, and Cell papers, and it'll be about waist high of all these new designs and synNotch receptors and all these other designs. I think one of the frustrating things for me was that—we were as guilty of this as the next person—we kept publishing more ways of curing mice, and it looked better, the doses were lower, and all of this—and of all that technology that was described, much of it remarkably elegant—very little of it has seeped into the realm of translational research, into clinical trials, and for better outcomes. That was actually a significant source of frustration for me because we were doing all of this and none of it was actually doing what it was intended to do, which was to translate.

Translating cell therapy, unlike drugs that can be manufactured en mass, is an expensive endeavor. So when I came to Roswell Park, the institution promised that they would build up their already existing cell therapy program and that the institution itself, through philanthropy, would support some of these early trials. Right now, there's very, very few grant mechanisms that would pay for a clinical trial, and that leaves you with philanthropy, institutional support, or both, or licensing to to to a company. I think that a lot of the venture capitalists have gotten pretty leery of funding cell therapy programs, not because I think there's anything fundamentally flawed about the concept of cell therapy for solid tumors, but I think there was kind of a wild west heyday where anything that had the word CAR-T in it they would throw money at and a lot of those have had very disappointing results.

So when I came to Roswell Park, there was funding provided through philanthropy. We have phenomenal philanthropy here in Buffalo and at Roswell Park that would allow us to translate some of these ideas into the clinical setting. In addition, we have in the 3 years since I got here now a 20-room good manufacturing practice (GMP) facility, which is the largest GMP facility where we can make these CAR T-cells for clinical trials. It's the largest of any academic institution in the country, which means that we have enough space that we can translate the work that we do in our labs, but even more so we can work with smaller biotechs and other pharmaceutical companies to run their clinical trials because we built out an entire infrastructure here in Buffalo that will allow us to do better at translating this work to the clinical setting.

So, if you ask what has been a shortcoming of the field? It's not innovation. It's not remarkably elegant and smart ways to overcome the limitations that we know now. It's that you hit this wall, which is $3 million to $5 million per clinical trial. What we've created here at Roswell—and I don't mean to overly plug the institution—but the institution, moreso than many, has been committed to moving this technology forward. Moving it forward doesn't mean getting better outcomes in your mice, it means getting better outcomes in your patients, and that requires a significant institutional commitment, it requires a creativity with how you utilize GMP space, and who you work with. I mean, ideally, we would love for the solutions that we come up with in our laboratories to be the next FDA-approved CAR T-cell treatment. But to a degree, neither us nor our patients really care where the idea comes from. If there are good ideas that we think are worthwhile translating into a clinical trial we are absolutely willing to work not just with our own investigators, but with with biotech companies, where we can carry out that translational process at a significantly reduced cost than if they had to go through private companies. We're excited about the fact that not only do we address what is lacking in getting this technology to work in solid tumors, but we're excited by the fact that we can actually move that stack of Cell, Nature, and Science papers into the clinic, and hopefully as a result translate those papers into New England Journal of Medicine papers. You gotta have faith.

This transcript has been edited for clarity.