CAR T Cells Targeting BAFF-R Can Overcome CD19 Antigen Loss in B Cell Malignancies

Overview

Journal Sci Transl Med

Specialties General Medicine
Science

Date 2019 Sep 27

PMID 31554741

Citations 48

Authors

Hong Qin

Zhenyuan Dong

Xiuli Wang

Wesley A Cheng

Feng Wen

Weili Xue

Han Sun

Miriam Walter

Guowei Wei

D Lynne Smith

Xiuhua Sun

Fan Fei

Jianming Xie

Theano I Panagopoulou

Chun-Wei Chen

Joo Y Song

Ibrahim Aldoss

Clarisse Kayembe

Luisa Sarno

Markus Muschen

Giorgio G Inghirami

Stephen J Forman

Larry W Kwak

Affiliations

Soon will be listed here.

Abstract

CAR T cells targeting CD19 provide promising options for treatment of B cell malignancies. However, tumor relapse from antigen loss can limit efficacy. We developed humanized, second-generation CAR T cells against another B cell-specific marker, B cell activating factor receptor (BAFF-R), which demonstrated cytotoxicity against human lymphoma and acute lymphoblastic leukemia (ALL) lines. Adoptively transferred BAFF-R-CAR T cells eradicated 10-day preestablished tumor xenografts after a single treatment and retained efficacy against xenografts deficient in CD19 expression, including CD19-negative variants within a background of CD19-positive lymphoma cells. Four relapsed, primary ALLs with CD19 antigen loss obtained after CD19-directed therapy retained BAFF-R expression and activated BAFF-R-CAR, but not CD19-CAR, T cells. BAFF-R-CAR, but not CD19-CAR, T cells also demonstrated antitumor effects against an additional CD19 antigen loss primary patient-derived xenograft (PDX) in vivo. BAFF-R is amenable to CAR T cell therapy, and its targeting may prevent emergence of CD19 antigen loss variants.

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