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Finding the Keys to the CAR: Identifying Novel Target Antigens for T Cell Redirection Immunotherapies

1
Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
2
Institute for Molecular Science, La Trobe University, Bundoora, VIC 3086, Australia
3
Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(2), 515; https://doi.org/10.3390/ijms21020515
Received: 28 November 2019 / Revised: 8 January 2020 / Accepted: 9 January 2020 / Published: 14 January 2020
(This article belongs to the Special Issue CAR-T Cell Therapy)
Oncology immunotherapy has been a significant advancement in cancer treatment and involves harnessing and redirecting a patient’s immune response towards their own tumour. Specific recognition and elimination of tumour cells was first proposed over a century ago with Paul Erlich’s ‘magic bullet’ theory of therapy. In the past decades, targeting cancer antigens by redirecting T cells with antibodies using either bispecific T cell engagers (BiTEs) or chimeric antigen receptor (CAR) T cell therapy has achieved impressive clinical responses. Despite recent successes in haematological cancers, linked to a high and uniformly expressed CD19 antigen, the efficacy of T cell therapies in solid cancers has been disappointing, in part due to antigen escape. Targeting heterogeneous solid tumours with T cell therapies will require the identification of novel tumour specific targets. These targets can be found among a range of cell-surface expressed antigens, including proteins, glycolipids or carbohydrates. In this review, we will introduce the current tumour target antigen classification, outline existing approaches to discover novel tumour target antigens and discuss considerations for future design of antibodies with a focus on their use in CAR T cells. View Full-Text
Keywords: chimeric antigen receptor T cells (CAR T); Bi-specific T cell Engager (BiTE); immunotherapy; oncology; antigen selection; target antigen; proteomics; glycomics; lipidomics; antigenic screen; cell surface antigen; phage display chimeric antigen receptor T cells (CAR T); Bi-specific T cell Engager (BiTE); immunotherapy; oncology; antigen selection; target antigen; proteomics; glycomics; lipidomics; antigenic screen; cell surface antigen; phage display
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Abbott, R.C.; Cross, R.S.; Jenkins, M.R. Finding the Keys to the CAR: Identifying Novel Target Antigens for T Cell Redirection Immunotherapies. Int. J. Mol. Sci. 2020, 21, 515.

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