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.
Highlights
High precision tumour targeting has been revolutionised by the emergence of T cell based immunotherapies utilising the infusion of activated, genetically engineered T cells, or by delivery of bispecific T cell engaging antibodies (BiTEs) [1]
Novel, personalised treatment approaches such as immunotherapy offer the advantage of targeting cancer cells, one of the major hurdles to the implementation of immunotherapy is the identification of new targets to widen therapeutic clinical options
Transcriptomics and bioinformatics outlined in this review offer a path forward for the discovery of novel targets for use in immunotherapy
Summary
High precision tumour targeting has been revolutionised by the emergence of T cell based immunotherapies utilising the infusion of activated, genetically engineered T cells, or by delivery of bispecific T cell engaging antibodies (BiTEs) [1]. Despite several potential solid tumour targets being investigated, there has been limited reports of long term responses [14] Both BiTEs and CAR T cells offer an exciting possibility to redirect a patient’s endogenous T cells to induce antitumour activity, and these two forms of immunotherapy have been recently excellently contrasted and reviewed [15]. Systematic target antigen selection may be critical to overcoming the challenges associated with antigen escape, and treatment of solid tumours [22] Tcell redirection immunotherapies, such as CARs and BiTEs are capable of inducing a reduction in cancer burden—evident by the success in treating some forms of haematological cancers. We discuss the current approaches used to identify novel targets for therapeutic development for T cell redirection immunotherapy
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