February 27, 2020
Michael Wang, MD

CAR T-Cell Therapy, and MCL’s future management

Michael Wang, MD, The University of Texas MD Anderson Cancer Center

Michael Wang, MD, The University of Texas MD Anderson Cancer Center:  Chemotherapy and chemotherapy-free therapy include the best combinations of ibrutinib and acalabrutinib-zanubrutinib. They can not cure a patient with T-cell therapies for CAR [chimeric antigen receptor]. Cell therapies, CAR T-cell therapy— what’s involved? You take the patient’s own blood, draw it, take the T cells, put it in the lab, and then use a vial to carry the virus. This is not harmful, but it can carry the gene into the cell and transfer the T cells so that the gene is expressed above the T cells. This is the chimeric antigen receptor. This chimeric goes into the antigen. The antigen is in the lymphoma cells. Now you have the chimeric antigen, and the T cells are able to recognize these lymphoma cells. But before you do that, you amplify the CAR T cells, the chimeric antigen T cells, and then you put it back. Not only can T cells recognize lymphoma cells or tumor cells, but they can also be more numerous. Well, that’s the best therapy. Even the very harsh lymphomas that we can treat now. They zoom in through the chemotherapy. You’re giving them all the targeted therapies. They just grow monster lymphomas, and boom — we can kill them with cell therapy.

Michael Wang said “In the case of mantle cell lymphoma, I’m going to present the ZUMA-2 study this afternoon, and it’s a huge event, very anticipated, especially by our patients and their families. Mantle cell lymphoma is rare. Large-cell lymphoma is very common, so CAR T-cell therapy for large-cell lymphoma was approved 2 years ago. While the large cell lymphoma is benefiting, a lot of patients are in remission. Patients with mantle cell lymphoma sometimes don’t make it. I feel the pressure; they feel the pressure; they feel the pressure. This presentation, which is very much linked to the approval of the FDA, is a much-anticipated event.”

He also said, “In fact, we have already published the abstract for this Annual Meeting & Exhibition of the ASH American Society of Hematology. The response rate is already over 80%. The CR total response rate is only 53%—we already have 60 patients. In the abstract, we can only describe 28 patients, and 28 patients have already been fantastic. I will describe the 460 patients in my presentation.”

Michael Wang said, “According to Chemotherapy targeted therapy, we are in this era. How about the future? What if some of the CAR T-cell therapies and these 3 modalities are unable to cure them? In the future, we are looking into the precision medicine era. I am very proud that I have been a co-principal investigator for the University of Texas MD Anderson Cancer Center Moon Shot project on B-cell lymphoma for the past 5 years. We use chemotherapy, targeted therapy, immunotherapy, cell therapies, CAR T-cell therapies— cell therapy is not just CAR T. We developed natural killer cell therapies with Moon Shot CAR NK, which were very good. The direction we’re heading in is the era of precision medicine. We’re looking at precision medicine in a few years after CAR T-cell therapy. What is the precision of this? We sequence all the tumors. We not only sequence but also include DNA, RNA, proteomics, epigenetics. We also study each patient’s biological mechanism. Why are they resistant to all these therapies? Using all the sequence data, the biological mechanism, the best technology, we could decipher and then find our Achilles ‘ heel of each resistant tumour and then kill it, attack that Achilles ‘ heel with the exact medicine needed there. We do not need to use so many. This is the future of the era of precision medicine. There’s never been a better time to be an academic haematologist. It’s never a good time to get a diagnosis of lymphoma, but this area is growing so much, and it’s very exciting. I wake up very excited every morning.”

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