Antitumor efficacy of BAFF-R targeting CAR T cells manufactured under clinic-ready conditions

Zhenyuan Dong, Wesley A. Cheng, D. Lynne Smith, Brian Huang, Tiantian Zhang, Wen Chung Chang, Xiuli Wang, Stephen J. Forman, Larry W. Kwak, Hong Qin

Research output: Contribution to journalArticlepeer-review

Abstract

B-cell malignancies can potentially be cured by CD19 chimeric antigen receptor (CAR) T-cell therapy. Although clinical response rates can be up to 93% in acute lymphoblastic leukemia, treatment-related antigen loss and lack of therapeutic persistence contribute to disease relapse. These shortcomings of current CAR T-cell therapy indicate the need for biologically relevant target selection and for improving the efficacy and persistence of the CAR T cells, which we have addressed by developing a novel B-cell activating factor receptor (BAFF-R) CAR T-cell therapy with improved therapeutic persistence. BAFF-R is a B-cell survival receptor and highly expressed in B-cell malignancies. We developed a prototype CAR T cell that efficiently and specifically eliminated BAFF-R expressing human B-cell tumors in several xenogeneic mouse models, including models of CD19 antigen loss. We proceeded with translational development and validation of BAFF-R CAR T cells produced under current good manufacturing practices (cGMP). cGMP-grade BAFF-R CAR T cells underwent in vitro and in vivo validation in established models to confirm that the potency and efficacy of our original research modeling was replicated. Food and Drug Administration required release testing was performed to ensure our BAFF-R CAR T cells meet specifications for new drug products. Completing and exceeding these requirements, the data fully support the initiation of a first-in-human Phase 1 trial for BAFF-R-positive relapsed/refractory (r/r) B-ALL.

Original languageEnglish (US)
Pages (from-to)2139-2145
Number of pages7
JournalCancer Immunology, Immunotherapy
Volume69
Issue number10
DOIs
StatePublished - Oct 1 2020

Keywords

  • Acute lymphoblastic leukemia
  • BAFF-R
  • CAR T cell therapy
  • GMP production

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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