CD20-CD19 Bispecific CAR T Cells for the Treatment of B-Cell Malignancies

Hum Gene Ther. 2017 Dec;28(12):1147-1157. doi: 10.1089/hum.2017.126.


The treatment of leukemia/lymphoma by chimeric antigen receptor (CAR) redirected T cells with specificity for CD19 induced complete remissions in the majority of patients, with a realistic hope for cure. However, recent follow-up data revealed a substantial risk of relapse through leukemic cells that lack the CAR targeted antigen. In this situation, a bispecific CAR with binding domains for CD19 and CD20 is aimed at recognizing leukemic cells with only one cognate antigen. The anti-CD20-CD19 bispecific CAR induced a full T-cell response upon engagement of CD19 or CD20 on target cells showing a true "OR" gate recognition in redirecting T-cell activation. T cells with the anti-CD20-CD19 CAR efficiently killed patients' chronic lymphocytic leukemia cells in vitro. The bispecific CAR T cells cleared pediatric acute lymphocytic leukemia with a mixed CD19+CD20+/CD20- phenotype from the blood and bone marrow of transplanted mice, while anti-CD20 CAR T cells left CD20- leukemic cells behind without curing the disease. Data indicate the superior anti-leukemic activity in the control of leukemia, implying that the anti-CD20-CD19 bispecific CAR T cells may reduce the risk of relapse through antigen-loss leukemic cells in the long term.

Keywords: CAR; CD19; CD20; adoptive cell therapy; bispecific targeting; chimeric antigen receptor; leukemia; relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD19 / immunology*
  • Antigens, CD20 / immunology*
  • Cell Line, Tumor
  • Female
  • HEK293 Cells
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / therapy*
  • Male
  • Receptors, Antigen, T-Cell* / genetics
  • Receptors, Antigen, T-Cell* / immunology
  • Recombinant Fusion Proteins* / genetics
  • Recombinant Fusion Proteins* / immunology
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / transplantation


  • Antigens, CD19
  • Antigens, CD20
  • CD19 molecule, human
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins