A phase I study of loco-regional immunotherapy by transbronchial injection of α-galactosylceramide-pulsed antigen presenting cells in patients with lung cancer

Clin Immunol. 2020 Jun:215:108457. doi: 10.1016/j.clim.2020.108457. Epub 2020 May 6.

Abstract

We conducted a phase I study of the trans-bronchial injection of α-galactosylceramide (αGalCer)-pulsed antigen presenting cells (APCs) to evaluate their safety, immune responses, and anti-tumor activities. Patients with advanced or recurrent non-small cell lung cancer (NSCLC) refractory to standard treatments were eligible. αGalCer-pulsed APCs were administered intratumorally or intranodally by bronchoscopy. Twenty-one patients were enrolled in this study. No severe adverse events related to the cell therapy were observed during this study in any patient. After αGalCer-pulsed APCs were administrated, increased iNKT cell numbers were observed in PBMCs from eight cases, and IFN-γ producing cells were increased in the peripheral blood of 10 cases. Regarding clinical responses, one case exhibited a partial response and eight were classified as stable disease. In the tumor microenvironment, IFN-γ expression was upregulated after treatment in partial response or stable disease cases and TGF-β was upregulated in progressive disease cases.

Keywords: Antigen presenting cells; Bronchoscopy; Immunotherapy; Lung cancer; NKT cells.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antigen-Presenting Cells / immunology*
  • Bronchi / immunology*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Female
  • Galactosylceramides / administration & dosage*
  • Galactosylceramides / immunology*
  • Humans
  • Immunotherapy / methods
  • Interferon-gamma / immunology
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Natural Killer T-Cells / immunology
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / therapy
  • Tumor Microenvironment / immunology

Substances

  • Galactosylceramides
  • alpha-galactosylceramide
  • Interferon-gamma

Associated data

  • UMIN-CTR/UMIN000005208