Phase I clinical trial of fibronectin CH296-stimulated T cell therapy in patients with advanced cancer

PLoS One. 2014 Jan 31;9(1):e83786. doi: 10.1371/journal.pone.0083786. eCollection 2014.

Abstract

Background: Previous studies have demonstrated that less-differentiated T cells are ideal for adoptive T cell transfer therapy (ACT) and that fibronectin CH296 (FN-CH296) together with anti-CD3 resulted in cultured cells that contain higher amounts of less-differentiated T cells. In this phase I clinical trial, we build on these prior results by assessing the safety and efficacy of FN-CH296 stimulated T cell therapy in patients with advanced cancer.

Methods: Patients underwent fibronectin CH296-stimulated T cell therapy up to six times every two weeks and the safety and antitumor activity of the ACT were assessed. In order to determine immune function, whole blood cytokine levels and the number of peripheral regulatory T cells were analyzed prior to ACT and during the follow up.

Results: Transferred cells contained numerous less-differentiated T cells greatly represented by CD27+CD45RA+ or CD28+CD45RA+ cell, which accounted for approximately 65% and 70% of the total, respectively. No ACT related severe or unexpected toxicities were observed. The response rate among patients was 22.2% and the disease control rate was 66.7%.

Conclusions: The results obtained in this phase I trial, indicate that FN-CH296 stimulated T cell therapy was very well tolerated with a level of efficacy that is quite promising. We also surmise that expanding T cell using CH296 is a method that can be applied to other T- cell-based therapies.

Trial registration: UMIN UMIN000001835.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Anorexia / etiology
  • CD28 Antigens / immunology
  • CD28 Antigens / metabolism
  • Cytokines / immunology
  • Cytokines / metabolism
  • Fatigue / etiology
  • Female
  • Fibronectins / immunology*
  • Follow-Up Studies
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods
  • Leukocyte Common Antigens / immunology
  • Leukocyte Common Antigens / metabolism
  • Male
  • Middle Aged
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Recombinant Proteins / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / transplantation
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Thrombocytopenia / etiology
  • Treatment Outcome
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism

Substances

  • CD28 Antigens
  • Cytokines
  • Fibronectins
  • Recombinant Proteins
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • retronectin
  • Leukocyte Common Antigens

Grants and funding

This study was partially supported by JSPS KAKENHI Grant Number 23590891. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study.