In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 7 ( 2020-04-01), p. 1606-1615
Abstract:
Immunogenicity derived from the murine scFv, a major molecular compomemt of chimeric antigen receptors (CARs), may limit the persistence of CAR T cells, resulting in tumor relapse of patients in complete remission (CR). In this study, we developed a humanized anti-CD19 scFv CAR-T (hCAR-T) to treat patients with relapsed/refractory acute lymphoblastic leukemia (r/r ALL). Patients and Methods: In this one-arm, open-labeled study, we infused the T cells modified with hCAR to patients with r/r ALL. Patients were evaluated with long-term follow-up for response and safety of the treatment. The study was registered at Clinicaltrials.gov (NCT02349698). Results: Ten patients with r/r ALL were recruited for this study. All were response evaluable and all achieved CR; eight patients remained CR, and six were in CR for over 18 months without further treatment. A long-term persistence of hCAR T cells was observed in most of the patients. Among these patients, four of them with high tumor burden and rapidly progressive disease (median, 58%) experienced grade 3–4 cytokine release syndrome (CRS) and neurotoxicity. These severe CRSs were successfully controlled by tocilizumab, glucocorticoid, and plasma exchange. Conclusions: T cells expressing the humanized anti-CD19 scFv CARs exhibited sustained therapeutic efficacy in the treatment of r/r ALL. Low replase rate was associated with the long-term persistence of CAR T cells.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-19-1339
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2020
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
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