Volume 2 Supplement 2

Abstracts from the 1st Immunotherapy of Cancer Conference (ITOC1)

Open Access

P71. Adoptive transfer of TCR gene-transduced lymphocytes targeting MAGE-A4 for refractory esophageal cancer

  • H Shiku1,
  • H Ikeda1,
  • Y Miyahara1,
  • M Ishihara2,
  • N Katayama2,
  • D Tomura3,
  • I Nukaya3,
  • J Mineno3,
  • K Takesako3 and
  • S Kageyama1
Journal for ImmunoTherapy of Cancer20142(Suppl 2):P45

DOI: 10.1186/2051-1426-2-S2-P45

Published: 12 March 2014

Background

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 extend the application of adoptive T cell therapy for cancer patients. However, this concept has not been tested in the epithelial cancer patients.

Materials and methods

MAGE-A4-specific TCR α and β chains were cloned from a human T cell clone that recognises MAGE-A4143-151 peptide in a HLA-A*24:02 restricted manner. This T cell clone did not show any cross reactivity to the peptides with homology to the MAGE-A4143-151 epitope. A retroviral vector that encodes these TCR chains without any artificial modification was constructed; the lymphocytes transduced with the retroviral vector killed the MAGE-A4 expressing tumor in vitro and inhibited the tumour growth in the NOG immunodeficient mice.

A phase I clinical trial of TCR gene therapy targeting MAGE-A4 was performed to treat refractory esophageal cancer patients without lympho-depleting pre-conditioning. The trial was designed as a cell-dose escalation consisting of three cohorts, 2x108, 1x109 and 5x109 cells/patient. Vaccines with the cognate peptide were also given following adoptive transfer of lymphocytes on day 14 and day 28.

Results

The treatment was tolerable with no adverse events associated with transferred cells or any viral toxicity. 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 transferred lymphocytes that were harvested from the patients more than 50 days after the transfer were found to sustain the reactivity to the antigen-expressing tumour cells. Three patients showed SD or long tumour free status.

Conclusions

This approach may extend the availability of adoptive T cell therapy for epithelial cancer patients by providing tumour-reactive and long surviving lymphocytes.

Authors’ Affiliations

(1)
Cancer Vaccine and Immuno-Gene Therapy, Mie University Graduate School of Medicine
(2)
Hematology and Oncology, Mie University Graduate School of Medicine
(3)
Takara Bio Inc., Center for Cell and Gene Therapy

Copyright

© Shiku et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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