Abstract 2805: Cancer-specific T cell receptor isolation for cancer immunotherapy

Malignant cells may be recognized by T cells binding cell surface Class I HLA-peptide complexes presenting disease-associated epitopes. Many cancer patients generate CD8 cytotoxic T cell responses to tumor-associated antigens, however due to the low avidity of these T cells and cancer cells developing escape mechanisms for avoiding destruction by T cells, the immune system fails to clear tumors. 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 tumor 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-tumor T cell response. In order to produce ImmTACs, we have developed an integrated in-house process leading to the isolation of TCRs specific for validated cancer epitopes. The critical steps in this process are: antigen selection, epitope identification, T cell cloning, TCR isolation and binding to soluble peptide:MHC on the BIAcore. We describe each of these steps in more detail and present data to illustrate the successful isolation of a number of TCRs specific for various tumor associated antigens such as prostate and cancer testis antigens leading from this procedure. Citation Format: Luise U. Weigand, Samantha Paston, Linda Hibbert, Ruth K. Ryan, Debbie E. Baker, Ruth A. Simmons, Jane V. Harper, Joseph D. Dukes, Giovanna Bossi, Francis Grand, Emma Hickman, Alex Powlesland, Annelise Vuidepot, Namir J. Hassan, Bent K. Jakobsen. Cancer-specific T cell receptor isolation for cancer immunotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2805. doi:10.1158/1538-7445.AM2014-2805