Article Text

Download PDFPDF

In vivo persistence of adoptively transferred TCR gene-transduced lymphocytes with anti-tumor reactivity in patients with MAGE-A4 expressing esophageal cancer
  1. Hiroaki Ikeda1,
  2. Shinichi Kageyama1,
  3. Naoko Imai1,
  4. Yoshihiro Miyahara1,
  5. Mikiya Ishihara1,
  6. Naoyuki Katayama2,
  7. Hirofumi Yoshioka3,
  8. Daisuke Tomura3,
  9. Ikuei Nukaya3,
  10. Junichi Mineno3,
  11. Kazuto Takesako3 and
  12. Hiroshi Shiku1
  1. Aff1 grid.260026.0000000040372555XDepartment of Immuno-Gene TherapyMie University Graduate School of Medicine Mie, Tsu Japan
  2. Aff2 grid.260026.0000000040372555XDepartment of Hematology and OncologyMie University Graduate School of Medicine Mie, Tsu Japan
  3. Aff3 grid.410820.fCenter for Cell and Gene TherapyTakara Bio Inc. Shiga Japan

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Meeting abstracts

The application of adoptive immunotherapy with tumor-specific T cells has been limited because of the short life span of the transferred T cells unless the host has been manipulated. Engineering the antigen receptor gene in patients’ lymphocytes is one promising strategy to create antigen-specific lymphocytes without senescent phenotypes. The strategy provides an opportunity to broaden the types of cancer to be treated. However, this concept has not been tested in the epithelial cancer patients. We completed a phase I clinical trial of TCR gene therapy targeting MAGE-A4 to treat esophageal cancer patients without lympho-depleting pre-conditioning. The trial was designed as a cell-dose escalation consisting of three cohorts, 2x10E8, 1x10E9 and 5x10E9 cells/patient. The treatment was tolerable with no adverse events associated with transferred cells. In all ten patients of the 3 cell-doses, the transferred lymphocytes were detected in their peripheral blood in a dose-dependent manner during the first 14 days. In 4 patients, the infused cells have been persisting more than 5 months after the transfer. The T cell clones were established from the transferred lymphocytes that were harvested more than 100 days after the transfer. These clones sustained the reactivity to the antigen-expressing tumor cells. Three patients showed SD or long tumor free status. These results suggest that this approach may extend the availability of adoptive T cell therapy for epithelial cancer patients by providing tumor-reactive and long surviving lymphocytes reducing the risk of intensive pre-treatments.