Nirav Shah, MD, Medical College of Wisconsin, Milwaukee, Wisconsin, discusses the future of cell therapies, specifically developments in treatments like CAR T-cell therapy, for patients with various types of B-cell malignancies.

These insights and data were presented at the 2024 Pan Pacific Lymphoma (PPL) Conference in Lahaina, Hawaii.

Transcript:

Hi, my name is Nirav Shah. I'm an associate professor of medicine at the Medical College of Wisconsin in Milwaukee. I recently just joined the Pan Pacific Lymphoma meeting where I spoke on the future of cell therapies.

A brief summary of what I discussed was looking at what's up and coming in cell therapy, specifically treatments like CAR T -cell therapy. We're very lucky right now. We have multiple CD19 autologous CAR T-cell products that are available for our patients right now with relapsed/refractory B-cell malignancies. But there's lots of innovation and changes into how we may develop cell therapies in the future. We talked about some of those options that are coming down the road.

First, we talked about autologous car CAR T-cell products and changes in manufacturing.There's been a move towards rapid manufacturing, so manufacturing the cells in a shorter period of time. This would decrease the vein-to-vein time between when patients are apheresed, and when they get the CAR T-cells delivered back to them. There's also some potential clinical benefits by shortening the manufacturing and actually producing a more favorable CAR T-cell product.

We talked about new targets in CAR-T beyond CD19. We talked about a single targeted CD22 CAR, which looks to be effective in those patients who are relapsing after a CD19 CAR-T, and that there's an ongoing multicenter trial throughout the United States enrolling patients with relapsed DLBCL who have progressed after CD19 CAR-T. We talked about advances on CD19 CAR-T with dual targeting.

We talked about some of the research that comes out of my own institution in our program using dual targeting. So, a CAR -T that not only targets CD19, but also target CD20, as a way to improve the activity of this CAR-T against B-cell malignancies that have more than 1 antigen present. Beyond that, we also talked about different ways to manufacture CAR-T.

Much of this conversation was about autologous T-cells. There's also a growing number of clinical trials using an allogeneic T-cell. Rather than making a CAR-T from the patient themselves, making a CAR-T from a healthy donor, and then using that to treat patients with relapsed B-cell malignancies.

There are several companies such as Caribou that has the CD-19 allogeneic platform with the PD1 knockout to make the T-cells more resistant to target malignancies. There's actually dual-targeted allogenic products that are targeting both CD19 and CD20. There are gamma-delta T-cell products being developed targeting the CD20 protein. These allogeneic products have the advantage of being off the shelf and readily available, and don't require manufacturing time because they can be made before the patient actually needs them.

In summary, it’s a really exciting time in cell therapy. Lots of different approaches are being investigated. They’re all trying to improve on the current technologies. I left my future predictions here. I think that autologous CAR-T products are still the standard-of-care in B-cell malignancies, and I could see a new target or a dual target such as CD22 being approved in the next couple of years. I think that allogeneic CAR T cells as we get more data may be an option for certain patients where they’re not able to wait for the manufacturing time, or are not able to manufacture for reasons that are out of the patient’s control.

I think the future is going to be developing the best CAR-T product for each patient and each specific disease. I was excited to share the progress up until that time at the Pan Pacific meeting.

Source:

Shah N. Future Therapies: Cellular Therapies. Presented at the 2024 Pan Pacific Lymphoma Conference. July 15–19, 2024; Lahaina, HI.