Checkpoint Blockade in Cancer Immunotherapy: Squaring the Circle

• Main Authors: Maria A.V. Marzolini, Sergio A. Quezada, Karl S. Peggs
• Format: Article
• Language: English
• Published: European Medical Journal 2015-03-01
• Series: European Medical Journal Oncology
• Subjects: Cancer immunotherapy; cytotoxic T lymphocyte associated antigen-4 (CTLA-4); programmed cell death protein-1 (PD-1); programmed death ligand-1 (PD-L1)
• Online Access: http://emjreviews.com/wp-content/uploads/Checkpoint-Blockade-in-Cancer-Immunotherapy-Squaring-the-Circle.pdf

Manipulating the complex interaction between the immune system and tumour cells has been the focus of cancer research for many years, but it is only in the past decade that significant progress has been made in the field of cancer immunotherapy resulting in clinically effective treatments. The blockade of co-inhibitory immune checkpoints, essential for maintaining lymphocyte homeostasis and self-tolerance, by immunomodulatory monoclonal antibodies has resulted in the augmentation of anti-tumour responses. The greatest successes so far have been seen with the blockade of cytotoxic T lymphocyte associated antigen-4, which has resulted in the first Phase III clinical trial showing an overall survival benefit in metastatic melanoma, and in the blockade of the programmed cell death protein-1 axis. This concise review will focus on the clinical advances made by the blockade of these two pathways and their role in current cancer treatment strategies.