Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19

Blood. 2010 Nov 18;116(20):4099-102. doi: 10.1182/blood-2010-04-281931. Epub 2010 Jul 28.

Abstract

Adoptive transfer of genetically modified T cells is an attractive approach for generating antitumor immune responses. We treated a patient with advanced follicular lymphoma by administering a preparative chemotherapy regimen followed by autologous T cells genetically engineered to express a chimeric antigen receptor (CAR) that recognized the B-cell antigen CD19. The patient's lymphoma underwent a dramatic regression, and B-cell precursors were selectively eliminated from the patient's bone marrow after infusion of anti-CD19-CAR-transduced T cells. Blood B cells were absent for at least 39 weeks after anti-CD19-CAR-transduced T-cell infusion despite prompt recovery of other blood cell counts. Consistent with eradication of B-lineage cells, serum immunoglobulins decreased to very low levels after treatment. The prolonged and selective elimination of B-lineage cells could not be attributed to the chemotherapy that the patient received and indicated antigen-specific eradication of B-lineage cells. Adoptive transfer of anti-CD19-CAR-expressing T cells is a promising new approach for treating B-cell malignancies. This study is registered at www.clinicaltrials.gov as #NCT00924326.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Antigens, CD19 / immunology*
  • B-Lymphocytes / cytology*
  • Cell Lineage / immunology*
  • Genetic Engineering*
  • Humans
  • Lymphocyte Depletion*
  • Lymphoma / immunology
  • Lymphoma / therapy*
  • Male
  • Receptors, Antigen / immunology
  • Remission Induction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Transduction, Genetic
  • Transplantation, Autologous

Substances

  • Antigens, CD19
  • Receptors, Antigen

Associated data

  • ClinicalTrials.gov/NCT00924326