Abstract
In recent years, much research has been focused on the field of adoptive cell therapies (ACT) that use native or genetically modified T cells as therapeutic tools. Immunotherapy with T cells expressing chimeric antigen receptors (CARs) demonstrated great success in the treatment of haematologic malignancies, whereas adoptive transfer of autologous tumour infiltrating lymphocytes (TILs) proved to be highly effective in metastatic melanoma. These encouraging results initiated many studies where ACT was tested as a treatment for various solid tumours. In this review, we provide an overview of the challenges of T cell-based immunotherapies of solid tumours. We describe alternative approaches for choosing the most efficient T cells for cancer treatment in terms of their tumour-specificity and phenotype. Finally, we present strategies for improvement of anti-tumour potential of T cells, including combination therapies.
Highlights
The two main approaches dominate T cell-based therapies of cancer
Upon recognition of a tumour-specific antigen or a tumour-associated antigen presented by a cancer cell, a cytotoxic CD8+ T cell activates and produces various proinflammatory cytokines, e.g., interferon γ (IFNγ), and releases perforin and granzymes, which lead to cancer cell death
chimeric antigen receptors (CARs) T cell therapy has been associated with life-threatening adverse effects, such as cytokine release syndrome resulting from massive CAR T cell activation [16]
Summary
The two main approaches dominate T cell-based therapies of cancer These strategies harness: (1) native or genetically engineered T cells with antigen-specific T cell receptor (TCR); or (2) T cells genetically modified to express chimeric antigen receptor (CAR). Due to its unique structure and function, TCR can recognise only peptides bound to major histocompatibility complex (MHC) molecules, while CARs can potentially bind various types of antigens ( peptides) and do not need MHC presentation. This can be an advantage in the case of MHC loss that is observed for many tumours [1]. CARs bind surface antigens only, whereas TCRs can recognise all types of tumour-specific proteins processed into peptides and presented on MHC molecules, including intracellular proteins that remarkably increases the number of potential peptide targets
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