T-Cell Receptor Stimulation Enhances the Expansion and Function of CD19 Chimeric Antigen Receptor-Expressing T Cells

Clin Cancer Res. 2019 Dec 15;25(24):7340-7350. doi: 10.1158/1078-0432.CCR-18-3199. Epub 2019 Sep 26.


Purpose: Current protocols for CD19 chimeric antigen receptor-expressing T cells (CD19.CAR-T cells) require recipients to tolerate preinfusion cytoreductive chemotherapy, and the presence of sufficient target antigen on normal or malignant B cells.

Patients and methods: We investigated whether additional stimulation of CD19.CAR-T cells through their native receptors can substitute for cytoreductive chemotherapy, inducing expansion and functional persistence of CD19.CAR-T even in patients in remission of B-cell acute lymphocytic leukemia. We infused a low dose of CD19.CAR-modified virus-specific T cells (CD19.CAR-VST) without prior cytoreductive chemotherapy into 8 patients after allogeneic stem cell transplant.

Results: Absent virus reactivation, we saw no CD19.CAR-VST expansion. In contrast, in patients with viral reactivation, up to 30,000-fold expansion of CD19.CAR-VSTs was observed, with depletion of CD19+ B cells. Five patients remain in remission at 42-60+ months.

Conclusions: Dual T-cell receptor and CAR stimulation can thus potentiate effector cell expansion and CAR-target cell killing, even when infusing low numbers of effector cells without cytoreduction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / physiology
  • Adolescent
  • Antigens, CD19 / immunology*
  • Antigens, CD19 / metabolism
  • Child
  • Child, Preschool
  • Genetic Vectors
  • Herpesvirus 4, Human / physiology
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / therapy*
  • Lymphoma, B-Cell / virology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / virology
  • Receptors, Antigen, T-Cell / immunology*
  • Retroviridae / physiology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • T-Lymphocytes / virology
  • Young Adult


  • Antigens, CD19
  • Receptors, Antigen, T-Cell