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

Abstract

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.

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