Journal
SCIENCE CHINA-LIFE SCIENCES
Volume 59, Issue 4, Pages 379-385Publisher
SCIENCE PRESS
DOI: 10.1007/s11427-016-5035-4
Keywords
chimeric antigen receptor T cells; B-cell acute lymphoblastic leukemia; biomarker; immunosurveillance; microenvironment
Categories
Funding
- National Science Foundation for Young Scientists of China [81402567, 81402566, 81472612]
- Bejing Nova Program [XX2016086]
- China Postdoctoral Science Foundation Grant [201150M1533]
- Science and Technology Planning Project of Beijing City [Z151100003915076]
- National Natural Science Foundation of China [31270820, 81230061]
- People's Republic of China Support Fund [2015PC-TSYS-2013]
Ask authors/readers for more resources
Anti-CD19 chimeric antigen receptor-modified T (CAR-T-19) cells have emerged as a powerful targeted immunotherapy for B-cell lineage acute lymphoblastic leukemia with a remarkable clinical response in recent trials. Nonetheless, few data are available on the subsequent clinical monitoring and treatment of the patients, especially those with disease recurrence after CAR-T-19 cell infusion. Here, we analyzed three patients who survived after our phase I clinical trial and who were studied by means of biomarkers reflecting persistence of CAR-T-19 cells in vivo and predictive factors directing further treatment. One patient achieved 9-week sustained complete remission and subsequently received an allogeneic hematopoietic stem cell transplant. Another patient who showed relapse after 20 weeks without detectable leukemia in the cerebrospinal fluid after CAR-T-19 cell treatment was able to achieve a morphological remission under the influence of stand-alone low-dose chemotherapeutic agents. The third patient gradually developed extensive extramedullary involvement in tissues with scarce immune-cell infiltration during a long period of hematopoietic remission after CAR-T-19 cell therapy. Long-term and discontinuous increases in serum cytokines (mainly interleukin 6 and C-reactive protein) were identified in two patients (Nos. 1 and 6) even though only a low copy number of CAR molecules could be detected in their peripheral blood. This finding was suggestive of persistent functional activity of CAR-T-19 cells. Combined analyses of laboratory biomarkers with their clinical manifestations before and after salvage treatment showed that the persistent immunosurveillance mediated by CAR-T-19 cells would inevitably potentiate the leukemia-killing effectiveness of subsequent chemotherapy in patients who showed relapse after CAR-T-19-induced remission.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available