Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia

Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia

August 25, 2011 | David L. Porter, M.D., Bruce L. Levine, Ph.D., Michael Kalos, Ph.D., Adam Bagg, M.D., and Carl H. June, M.D.
A lentiviral vector was used to create chimeric antigen receptor (CAR) T cells specific for CD19, a B-cell antigen. These CAR T cells were infused into a patient with refractory chronic lymphocytic leukemia (CLL), leading to a 1000-fold increase in their numbers in the body. The patient experienced a delayed onset of tumor lysis syndrome and achieved complete remission. CAR T cells persisted in the blood and bone marrow for six months, with continued expression of the CAR. The patient showed no detectable B cells or leukemia cells expressing CD19 in the bone marrow. Hypogammaglobulinemia was a chronic side effect. The CAR T cells expanded and persisted due to the inclusion of CD137 (4-1BB) signaling domains, which enhanced their survival and antitumor activity. The study highlights the potential of CAR T-cell therapy for B-cell malignancies, with the ability to induce long-term remission and sustained tumor control. The findings suggest that genetically modified autologous T cells may offer a new approach for treating CLL, particularly in patients with TP53 deletions, who typically have short remissions with standard therapies. The study also notes the importance of monitoring for toxic effects such as lymphopenia and tumor lysis syndrome. The results support further research into CAR T-cell therapy for B-cell neoplasms.A lentiviral vector was used to create chimeric antigen receptor (CAR) T cells specific for CD19, a B-cell antigen. These CAR T cells were infused into a patient with refractory chronic lymphocytic leukemia (CLL), leading to a 1000-fold increase in their numbers in the body. The patient experienced a delayed onset of tumor lysis syndrome and achieved complete remission. CAR T cells persisted in the blood and bone marrow for six months, with continued expression of the CAR. The patient showed no detectable B cells or leukemia cells expressing CD19 in the bone marrow. Hypogammaglobulinemia was a chronic side effect. The CAR T cells expanded and persisted due to the inclusion of CD137 (4-1BB) signaling domains, which enhanced their survival and antitumor activity. The study highlights the potential of CAR T-cell therapy for B-cell malignancies, with the ability to induce long-term remission and sustained tumor control. The findings suggest that genetically modified autologous T cells may offer a new approach for treating CLL, particularly in patients with TP53 deletions, who typically have short remissions with standard therapies. The study also notes the importance of monitoring for toxic effects such as lymphopenia and tumor lysis syndrome. The results support further research into CAR T-cell therapy for B-cell neoplasms.
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[slides and audio] Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia.