David Maloney, MD, PhD
The oncology community saw the first FDA approval of a chimeric antigen receptor (CAR) T-cell therapy in August 2017, when tisagenlecleucel (Kymriah) was approved for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refectory or in second or later relapse.
that was conducted between the time of these 2 approvals, David G. Maloney, MD, PhD, a member of the Clinical Research Division, Fred Hutchinson Cancer Research Center, discussed the progress made with CAR T cells, as well as the challenges that still exist in the use of this therapy.
OncLive: Can you discuss the success that has been seen with CAR T-cell therapy in ALL?
We are doing most of our research in CAR T cells, and that is what I am the most interested in. The process for a CAR gene-modified T cell is that we take out a patient’s normal resting T cells and separate them in the laboratory into different populations and transduce them with a lentivirus expressing a CAR. That CAR gene now makes an antibody transgene on the cell surface that can then bind the T cell to whatever the target is.
Obviously, we are doing studies in adults, as well. Toxicities are probably a little greater, but [it is] probably manageable. It is personalized medicine; the manufacturer now has to be in line with the patient to be able to make a product from that patient's cells. You clearly need an experienced team to be able to deal with CRS, and you need an intensive care unit (ICU) team to be able to take care of these patients when they get sick. Overall, [it is] a very exciting time, and now we are trying to translate it to other cancers—breast cancer, lung cancer, and other hematologic malignancies.
Let’s continue on that statement. Could the successes that we have seen with CAR T-cell therapies in ALL be translated to other malignancies?
It will be translated, but each [disease is different]. Antibody-drug conjugates are being used in other diseases already, and bispecific antibodies are not clear—they are active in lymphoma but we are unsure about solid cancers. In solid malignancies, CAR T cells have not been very effective to date; however, the studies are very, very limited at this point. The environment is very inhospitable for CAR T cells in a tumor mass; we are not even sure if they can get in there.
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