Abstract
Significant advances have been made to identify effective therapies that either restore or generate de novo a patient’s immune response to cancer, so-called immunotherapy or immuno-oncology (IO) therapies. Some tumors overcome immune surveillance by promoting mechanisms to evade or suppress the immune system. This conference report highlights the clinical promise and current challenges of IO therapy, including the use of immune-checkpoint antagonist monoclonal antibodies. Furthermore, this report investigates advances in preclinical modeling of cancer immunobiology and how this is helping our understanding of which patients will receive clinical benefits from current immune-checkpoint treatment. Looking to the future, the report looks at emerging IO approaches, which aim to specifically target the tumor microenvironment. This includes the use of toll-like receptors (TLRs) agonists that link the activation of innate immune, cells to the priming of T cells and an adaptive memory anti-tumor immune response through to the reversal of local immunosuppression using adenosinergic and indoleamine 2,3-dioxygenase (IDO) inhibitors.
Highlights
INTRODUCTIONThe promising anti-tumor activity of monoclonal antibodies (mAbs) targeting the immune-checkpoint proteins, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1), and the PD-1 ligand (PD-L1), led to regulatory approvals of these agents for the treatment of a variety of malignancies
On 27th–30th June 2017, the 4th International Therapeutic Tolerance Workshop: First-in-Human Data was hosted by Newcastle University Institute of Cellular Medicine, UK
The most clinically advanced immuno-oncology (IO) therapies are monoclonal antibodies that modulate the activity of T cells, by blocking inhibitory pathways that act as immunological checkpoints
Summary
The promising anti-tumor activity of mAbs targeting the immune-checkpoint proteins, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1), and the PD-1 ligand (PD-L1), led to regulatory approvals of these agents for the treatment of a variety of malignancies. The first of these drugs to be approved in 2011 was the anti-CTLA-4 antibody Ipilimumab (Yervoy®, Bristol-Myers Squibb) for the treatment of unresectable or metastatic melanoma [1]. Clinical data with anti-PD-L1 antibody, durvalumab (Imfinzi®, MEDI4736), led to the approval for this drug in 2017 for the treatment of previously treated patients with locally advanced or metastatic urothelial carcinoma [2]; further highlighting the potential of therapies that target immune evasion pathways
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