Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial

J Clin Oncol. 2021 Oct 20;39(30):3340-3351. doi: 10.1200/JCO.21.00389. Epub 2021 Jul 29.


Purpose: Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (r/r T-ALL) have few options and poor prognosis. The aim was to assess donor-derived anti-CD7 chimeric antigen receptor (CAR) T-cell safety and efficacy in patients with r/r T-ALL.

Methods: In this single-center, phase I trial, we administered anti-CD7 CAR T cells, manufactured from either previous stem-cell transplantation donors or new donors, to patients with r/r T-ALL, in single infusions at doses of 5 × 105 or 1 × 106 (±30%) cells per kilogram of body weight. The primary end point was safety with efficacy secondary.

Results: Twenty participants received infusions. Adverse events including cytokine release syndrome grade 1-2 occurred in 90% (n = 18) and grade 3-4 in 10% (n = 2), cytopenia grade 3-4 in 100% (n = 20), neurotoxicity grade 1-2 in 15% (n = 3), graft-versus-host disease grade 1-2 in 60% (n = 12), and viral activation grade 1-2 in 20% (n = 4). All adverse events were reversible, except in one patient who died through pulmonary hemorrhage related to fungal pneumonia, which occurred at 5.5 months, postinfusion. Ninety percent (n = 18) achieved complete remission with seven patients proceeding to stem-cell transplantation. At a median follow-up of 6.3 months (range, 4.0-9.2), 15 remained in remission. CAR T cells were still detectable in five of five patients assessed in month 6, postinfusion. Although patients' CD7-positive normal T cells were depleted, CD7-negative T cells expanded and likely alleviated treatment-related T-cell immunodeficiency.

Conclusion: Among 20 patients with r/r T-ALL enrolled in this trial, donor-derived CD7 CAR T cells exhibited efficient expansion and achieved a high complete remission rate with manageable safety profile. A multicenter, phase II trial of donor-derived CD7 CAR T cells is in progress (NCT04689659).

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD7 / immunology*
  • Cell- and Tissue-Based Therapy
  • Child
  • Child, Preschool
  • Cytokine Release Syndrome / etiology
  • Cytomegalovirus Infections / etiology
  • Epstein-Barr Virus Infections / etiology
  • Female
  • Graft vs Host Disease / etiology
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Lymphocyte Count
  • Lymphopenia / etiology
  • Male
  • Neutropenia / etiology
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Receptors, Chimeric Antigen / immunology*
  • Remission Induction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation*
  • Thrombocytopenia / etiology
  • Tissue Donors
  • Transplantation, Homologous / adverse effects
  • Virus Activation
  • Young Adult


  • Antigens, CD7
  • Receptors, Chimeric Antigen

Associated data

  • ChiCTR/ChiCTR2000034762