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Clin Immunol. 2014 Dec;155(2):160-75. doi: 10.1016/j.clim.2014.10.002. Epub 2014 Oct 16.

Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells.

Author information

1
Department of Immunology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, China.
2
Department of Bio-therapeutic, Chinese PLA General Hospital, China.
3
Department of Geriatric Hematology, Chinese PLA General Hospital, China.
4
Department of Hematology, Chinese PLA General Hospital, China.
5
Department of Immunology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, China. Electronic address: hanwdrsw69@yahoo.com.

Abstract

We conducted a trial testing a CD20-specific CAR coupled with CD137 and the CD3ΞΆ moiety in patients with chemotherapy refractory advanced diffuse large B cell lymphomas (DLBCL). Seven patients were enrolled. One of the two patients with no bulky tumor obtained a 14-month durable and ongoing complete remission by cell infusion only, and another attained a 6-month tumor regression. Four of five patients with bulky tumor burden were evaluable for clinical efficacy, three of which attained 3- to 6-month tumor regression. Delayed toxicities related to cell infusion are directly correlated to tumor burden and tumor-harboring sites, and mainly included cytokine release symptoms, tumor lysis symptoms, massive hemorrhage of the alimentary tract and aggressive intrapulmonary inflammation surrounding extranodal lesions. These results show firstly that anti-CD20 CART cells can cause prolonged tumor regression in combination with debulking conditioning regimens for advanced DLBCL. This study is registered at www.clinicaltrials.gov as NCT01735604.

KEYWORDS:

Anti-CD20 chimeric antigen receptor (CAR) T cells;; Delayed toxicities; Diffuse large B-cell lymphoma (DLBCL);; Refractory advanced;

PMID:
25444722
DOI:
10.1016/j.clim.2014.10.002
[Indexed for MEDLINE]

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