NNKTT120, an anti-iNKT cell monoclonal antibody, produces rapid and sustained iNKT cell depletion in adults with sickle cell disease

PLoS One. 2017 Feb 2;12(2):e0171067. doi: 10.1371/journal.pone.0171067. eCollection 2017.


Invariant NKT (iNKT) cells can be activated to stimulate a broad inflammatory response. In murine models of sickle cell disease (SCD), interruption of iNKT cell activity prevents tissue injury from vaso-occlusion. NKTT120 is an anti-iNKT cell monoclonal antibody that has the potential to rapidly and specifically deplete iNKT cells and, potentially, prevent vaso-occlusion. We conducted an open-label, multi-center, single-ascending-dose study of NKTT120 to determine its pharmacokinetics, pharmacodynamics and safety in steady-state patients with SCD. Doses were escalated in a 3+3 study design over a range from 0.001 mg/kg to 1.0 mg/kg. Twenty-one adults with SCD were administered NKTT120 as part of 7 dose cohorts. Plasma levels of NKTT120 predictably increased with higher doses. Median half-life of NKTT120 was 263 hours. All subjects in the higher dose cohorts (0.1 mg/kg, 0.3 mg/kg, and 1 mg/kg) demonstrated decreased iNKT cells below the lower limit of quantification within 6 hours after infusion, the earliest time point at which they were measured. In those subjects who received the two highest doses of NKTT120 (0.3, 1 mg/kg), iNKT cells were not detectable in the peripheral blood for a range of 2 to 5 months. There were no serious adverse events in the study deemed to be related to NKTT120. In adults with SCD, NKTT120 produced rapid, specific and sustained iNKT cell depletion without any infusional toxicity or attributed serious adverse events. The next step is a trial to determine NKTT120's ability to decrease rate of vaso-occlusive pain episodes.

Trial registration: clinicaltrials.gov NCT01783691.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sickle Cell / immunology*
  • Anemia, Sickle Cell / therapy*
  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Child
  • Cohort Studies
  • Female
  • Half-Life
  • Humans
  • Lymphocyte Depletion / methods*
  • Male
  • Natural Killer T-Cells / immunology*
  • Young Adult


  • Antibodies, Monoclonal, Humanized
  • NKTT120

Associated data

  • ClinicalTrials.gov/NCT01783691

Grant support

The study was funded by NKT Therapeutics Inc. NKT Therapeutics provided support in the form of salaries for RS and RM. JJF and DGN were consultants for NKT Therapeutics. The funders assisted in study design and data analysis. The funders helped to write and reviewed the manuscript for publication.