In Edinburgh, Scotland in September 2019, I had the opportunity to interview one of my doctors, Dr. David Maloney, who headed up my successful CAR-T trial at the Fred Hutch in Seattle, WA. I received my CAR-T cells in March 2018. David Maloney MD, PhD is Medical Director, Cellular Immunotherapy at the
Immunotherapy Integrated Research Center (IIRC), Fred Hutch, Seattle, WA.
First some vocabulary:
As CAR-T therapy is done now, cells are drawn from the patient and genetically modified outside of the body, then reinfused to seek and destroy the cancer.
This is called autologous, or from the same individual.
Allogeneic is the term used when the cells come from someone other than patients. This has been colloquially called “off the shelf” cells.
Takeaways:
- There are several potential advantages to allogeneic CAR-T or other genetically modified cells including:
- Less waiting for production. These are premade and ready to go. Like picking a sandwich from the deli counter, rather than having one made. This is less of an issue in CLL where we usually have time but is a major concern in fast moving acute leukemias, where saving a few days may be the difference between life and death.
- T cells from CLL patients, especially, can be pretty wimpy, having an “exhausted profile” and making them lousy foot soldiers in the fight against cancer. T cells from a healthy donor would be, well, healthy.
- There could be cost savings, like buying a bespoke suit versus one off the rack, but that is far from certain.
- It could address shortages of T cells.
- There are also several concerns about allogeneic cells:
- They may be rejected. Even the autologous cells are rejected as the body’s defenses recognizes the genetically changed receptors as foreign. There is research ongoing to snip out the “foreign” parts of the T cell so that they can be more invisible, but it is early.
- This is particularly important, as persistence of the CAR-T cells may be critical to their success.
- Natural killer (NK) cells are less likely to be rejected and there is reason to be hopeful that CAR-NK cells might be a good alternative for some patients, but again the trials are just beginning and there are zero long term data.
- There is a chance that the foreign CAR-T cells could attack the host, leading to Graft versus Host Disease (GVHD), a dreaded and common complication of allogeneic hematopoietic stem cell transplants (HSCT). The lack of GVHD risk is one of the big advantages of the present use of autologous cells for making CAR-Ts.
Conclusion:
Dr. Maloney is balanced in his analysis of the future direction of CAR-T cell therapy. More research is needed to work out the best path forward.
Please enjoy the video of my interview with Dr. Maloney at iwCLL 2019:
Thanks.
Stay strong. We are all in this together.
Brian Koffman
Dr. Brian Koffman, a well-known retired doctor, educator, and clinical professor turned patient has dedicated himself to teaching and helping the CLL community since his diagnosis in 2005. He serves as the Executive Vice President and Chief Medical Officer of the CLL Society Inc.
Originally published in The CLL Society Tribune CAR-T Special Edition.
