Autologous Versus Allogeneic CAR-T for the Near-Term Future

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

Renier Brentjens, MD, PhD
Credit: Roswell Park

Currently, all FDA approved chimeric antigen receptor T-cell (CAR-T) therapy products are based on the use of autologous alpha-beta (αβ) T-cells. Efforts to apply this technology to new indications, such as solid tumors, are ongoing, but so too are efforts to utilize CAR technology with allogeneic T-cells and other types of immune cells besides αβ T-cells

In an interview with Renier Brentjens, MD, PhD, the chair of the department of medicine and the deputy director at Roswell Park Comprehensive Cancer Center, CGTLive® asked Brentjens for his thoughts on the advantages of autologous versus allogeneic CAR T-cells. Brentjens used the analogy of an automobile (a "car") to make a point about perfecting the base technology of CARs before bringing in confounding variables.

CGTLive: What is your view on autologous versus allogeneic CAR-T approaches for the future?

Renier Brentjens, MD, PhD: I have a view on that. To carry the car analogy further, the first thing that you need to do when you design a car is have a good engine. The best way, I believe, that we're going to demonstrate how you design that engine is with autologous αβ T-cells. There are groups that are looking at CAR-natural killer (NK) cells, CAR gamma-delta T-cells, CAR macrophages—and all of that's fine and good and there's all rationales for using those. Also the question that you raised about off-the-shelf, allogeneic—all of these things are fine and good, but until you can demonstrate an autologous αβ T-cell that has none of those restrictions that any of these other cell types have—if you can demonstrate that you can design an engine for an autologous αβ T-cell that will be able to completely eradicate a solid tumor, I think that all of these other iterations, be it allogeneic, be it NK cells, etc.—I think those are a little bit like trying to design an air-conditioning or a stereo system for the car. Make it work first with the cell type that presents the fewest additional confounding variables, and that's an autologous αβ T-cell. Then once you've optimized it there, there's certainly virtue to having off-the-shelf products. It's probably going to be cheaper, it's probably going to be easier, and provide more access to more patients for this technology, but to start working on the seat belts and the air conditioning before you've optimized the engine, to me at least, philosophically doesn't make sense. So I am not trying to discourage any of my colleagues from looking at these other approaches. I simply think, on a very philosophical level, you need to first optimize it in the best situation possible and then you have the luxury of saying "okay, so let's take the optimal [situation] and let's see if we can convert that to off-the-shelf products or products that may have less toxicity, perhaps like these NK cells, etc."

This transcript has been edited for clarity.