• cancer
• immunotherapy
• CAR-T
• PD-1
• genetic modifications

Immunotherapy has emerged as one of the standard treatment modalities against cancer along with surgery, radiotherapy, chemotherapy and targeted therapy. Cancer immunotherapy harnesses the immune system to fight tumours, aiming at mounting effective antitumour immune responses. During the past few years, cancer immunotherapy has made great progress in two areas: immune checkpoint inhibitors and chimeric antigen receptor (CAR)-modified T cells (CAR-T). Other modalities of anticancer immunotherapy, including a variety of immunostimulatory monoclonal antibodies, small molecules that reverse cancer-associated immunosuppression and tumour-targeted therapeutic vaccines, are also studied in clinical trials.1 It is worth noting that the apparently rapid clinical advances reported in the past few years have benefited from decades of investment in basic science such as virology, immunology, cellular and molecular biology, and structural biology.

Cancer is not inherently highly immunogenic, and the tumour microenvironment (TME) can inhibit the activity of tumour-specific T cells. TME can use various strategies, collectively referred to as ‘immune evasion mechanisms’, to undermine the development of antitumour immunity and ultimately result in the failure of tumour growth control.2 The programmed cell death (PD) pathway, for instance, is one of the most characteristic immune evasion mechanisms. Once upregulated, it inhibits the antitumour responses of effector T cells and renders T cells dysfunctional. It has also been demonstrated that therapies blocking this pathway are effective in increasing the antitumour immune response in a variety of cancers.3

Immune checkpoint inhibitors are applied to eliminate the ‘brakes’ on the immune system that can impede immune cells from attacking cancer cells, among them are those targeting programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4).4 In 2018, Tasuku Honjo and …