A safe and potent anti-CD19 CAR T cell therapy

Nat Med. 2019 Jun;25(6):947-953. doi: 10.1038/s41591-019-0421-7. Epub 2019 Apr 22.


Anti-CD19 chimeric antigen receptor (CAR) T cell therapies can cause severe cytokine-release syndrome (CRS) and neurotoxicity, impeding their therapeutic application. Here we generated a new anti-CD19 CAR molecule (CD19-BBz(86)) derived from the CD19-BBz prototype bearing co-stimulatory 4-1BB and CD3ζ domains. We found that CD19-BBz(86) CAR T cells produced lower levels of cytokines, expressed higher levels of antiapoptotic molecules and proliferated more slowly than the prototype CD19-BBz CAR T cells, although they retained potent cytolytic activity. We performed a phase 1 trial of CD19-BBz(86) CAR T cell therapy in patients with B cell lymphoma (ClinicalTrials.gov identifier NCT02842138 ). Complete remission occurred in 6 of 11 patients (54.5%) who each received a dose of 2 × 108-4 × 108 CD19-BBz(86) CAR T cells. Notably, no neurological toxicity or CRS (greater than grade 1) occurred in any of the 25 patients treated. No significant elevation in serum cytokine levels after CAR T cell infusion was detected in the patients treated, including in those who achieved complete remission. CD19-BBz(86) CAR T cells persistently proliferated and differentiated into memory cells in vivo. Thus, therapy with the new CD19-BBz(86) CAR T cells produces a potent and durable antilymphoma response without causing neurotoxicity or severe CRS, representing a safe and potent anti-CD19 CAR T cell therapy.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD19 / genetics
  • Antigens, CD19 / immunology*
  • Cytokines / blood
  • Female
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods*
  • Lymphoma, B-Cell / diagnostic imaging
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / therapy*
  • Male
  • Middle Aged
  • Positron Emission Tomography Computed Tomography
  • Receptors, Chimeric Antigen / immunology*
  • Remission Induction
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • Young Adult


  • Antigens, CD19
  • CD19 molecule, human
  • Cytokines
  • Receptors, Chimeric Antigen

Associated data

  • ClinicalTrials.gov/NCT02842138