Autologous Nanobody-Derived Fratricide-Resistant CD7-CAR T-cell Therapy for Patients with Relapsed and Refractory T-cell Acute Lymphoblastic Leukemia/Lymphoma

Clin Cancer Res. 2022 Jul 1;28(13):2830-2843. doi: 10.1158/1078-0432.CCR-21-4097.


Purpose: Since CD7 may represent a potent target for T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) immunotherapy, this study aimed to investigate safety and efficacy of autologous CD7-chimeric antigen receptor (CAR) T cells in patients with relapsed and refractory (R/R) T-ALL/LBL, as well as its manufacturing feasibility.

Patients and methods: Preclinical phase was conducted in NPG mice injected with Luc+ GFP+CCRF-CEM cells. Open-label phase I clinical trial (NCT04004637) enrolled patients with R/R CD7-positive T-ALL/LBL who received autologous CD7-CAR T-cell infusion. Primary endpoint was safety; secondary endpoints included efficacy and pharmacokinetic and pharmacodynamic parameters.

Results: CD7 blockade strategy was developed using tandem CD7 nanobody VHH6 coupled with an endoplasmic reticulum/Golgi-retention motif peptide to intracellularly fasten CD7 molecules. In preclinical phase CD7 blockade CAR T cells prevented fratricide and exerted potent cytolytic activity, significantly relieving leukemia progression and prolonged the median survival of mice. In clinical phase, the complete remission (CR) rate was 87.5% (7/8) 3 months after CAR T-cell infusion; 1 patient with leukemia achieved minimal residual disease-negative CR and 1 patient with lymphoma achieved CR for more than 12 months. Majority of patients (87.5%) only had grade 1 or 2 cytokine release syndrome with no T-cell hypoplasia or any neurologic toxicities observed. The median maximum concentration of CAR T cells was 857.2 cells/μL at approximately 12 days and remained detectable up to 270 days.

Conclusions: Autologous nanobody-derived fratricide-resistant CD7-CAR T cells demonstrated a promising and durable antitumor response in R/R T-ALL/LBL with tolerable toxicity, warranting further studies in highly aggressive CD7-positive malignancies.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD7
  • Humans
  • Immunotherapy, Adoptive*
  • Mice
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma* / pathology
  • Receptors, Chimeric Antigen* / genetics
  • Receptors, Chimeric Antigen* / therapeutic use
  • Single-Domain Antibodies / therapeutic use


  • Antigens, CD7
  • Receptors, Chimeric Antigen
  • Single-Domain Antibodies

Associated data