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

Yao Wang; Wen-ying Zhang; Qing-wang Han; Yang Liu; Han-ren Dai; Ye-lei Guo; Jian Bo; Hui Fan; Yan Zhang; Ya-jing Zhang; Mei-xia Chen; Kai-chao Feng; Quan-shun Wang; Xiao-bing Fu; Wei-dong Han

doi:10.1016/j.clim.2014.10.002

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

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

Authors

Yao Wang¹, Wen-ying Zhang², Qing-wang Han¹, Yang Liu³, Han-ren Dai¹, Ye-lei Guo¹, Jian Bo⁴, Hui Fan², Yan Zhang², Ya-jing Zhang², Mei-xia Chen², Kai-chao Feng², Quan-shun Wang⁴, Xiao-bing Fu¹, Wei-dong Han⁵

Affiliations

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.

PMID: 25444722
DOI: 10.1016/j.clim.2014.10.002

Abstract

We conducted a trial testing a CD20-specific CAR coupled with CD137 and the CD3ζ 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;.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Antigens, CD20 / genetics
Antigens, CD20 / immunology*
Antigens, CD20 / metabolism
Cell Line
Combined Modality Therapy
Cytotoxicity, Immunologic
Female
Gene Dosage
Gene Order
Humans
Immunotherapy, Adoptive* / adverse effects
Lymphocyte Count
Lymphoma, Large B-Cell, Diffuse / diagnosis
Lymphoma, Large B-Cell, Diffuse / immunology*
Lymphoma, Large B-Cell, Diffuse / pathology
Lymphoma, Large B-Cell, Diffuse / therapy*
Magnetic Resonance Imaging
Male
Middle Aged
Neoplasm Staging
Positron-Emission Tomography
Protein Binding
Receptors, Antigen, T-Cell / genetics
Receptors, Antigen, T-Cell / immunology*
Receptors, Antigen, T-Cell / metabolism
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
T-Cell Antigen Receptor Specificity / immunology*
T-Lymphocytes / immunology*
T-Lymphocytes / metabolism*
Tomography, X-Ray Computed
Treatment Outcome
Tumor Necrosis Factor Receptor Superfamily, Member 9 / genetics
Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology
Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism

Substances

Antigens, CD20
Receptors, Antigen, T-Cell
Recombinant Fusion Proteins
Tumor Necrosis Factor Receptor Superfamily, Member 9

Associated data

ClinicalTrials.gov/NCT01735604