Volume 3 Supplement 2

30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015)

Open Access

Cancer-specific T cell receptor isolation for cancer immunotherapy

  • Debbie Emma Baker1,
  • Linda Hibbert1,
  • Luise Weigand1,
  • Samantha Paston1,
  • Ruth Ryan1,
  • Zoe Donnellan1,
  • Ruth Simmons1,
  • Kathy Hale1,
  • Louise Conlon1,
  • Joseph Dukes1,
  • Vanessa Clark1,
  • Caroline Boudousquie1,
  • Giovanna Bossi1,
  • Emma Hickman1,
  • Alex Powlesland1,
  • Annelise Vuidepot1,
  • Namir Hassan1 and
  • Bent Jakobsen1
Journal for ImmunoTherapy of Cancer20153(Suppl 2):P380

DOI: 10.1186/2051-1426-3-S2-P380

Published: 4 November 2015

Background

Malignant cells may be recognised by T cells binding cell surface Class I HLA (Human Leukocyte Antigen)-peptide complexes presenting disease-associated epitopes. Many cancer patients have been shown to generate CD8 cytotoxic T cell responses to tumour-associated antigens. However, this is often insufficient for the immune system to clear tumours, resulting in the progression of cancer. This is in part due to the low avidity of these T cells, as well as the ability of cancer cells to develop escape mechanisms to avoid destruction by T cells.

Methods

To overcome these issues, we have engineered novel, bi-functional protein therapeutics termed ImmTACs (Immune mobilising monoclonal TCR Against Cancer) which re-direct the immune system to target and destroy tumour cells with a high degree of potency and specificity. An ImmTAC comprises a high affinity ‘monoclonal’ T cell receptor (mTCR) targeting a cancer-associated HLA-peptide complex, fused to an anti-CD3 scFv domain which activates an anti-tumour T cell response.

Results

We have developed an integrated in-house process leading to the isolation of TCRs specific for validated cancer epitopes forming the starting material for ImmTAC production. The essential steps in this procedure are: antigen selection, epitope identification, T cell cloning, TCR isolation and binding to soluble peptide:MHC on the Biacore. High affinity ImmTACs are then generated through a process of affinity maturation.

Conclusions

The steps leading to the cloning of wild type TCRs are presented here, together with exemplary data to illustrate the successful isolation of TCRs resulting from this process.

Authors’ Affiliations

(1)
Immunocore Ltd.

Copyright

© Baker et al. 2015

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/4.0), 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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