Journal
MEDICINAL RESEARCH REVIEWS
Volume 40, Issue 2, Pages 654-682Publisher
WILEY
DOI: 10.1002/med.21632
Keywords
autoimmunity; CD28; CTLA-4; immune checkpoints; immunotherapy
Categories
Funding
- Canadian Institutes of Health Research [360929, 353953]
- Alberta Cancer Foundation [RES0025662]
- Li Ka Shing Applied Virology Institute at the University of Alberta [RES0028141]
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Modulation of T-cell immune functions by blocking key immune checkpoint protein interactions using monoclonal antibodies (mAbs) has been an innovative immunotherapeutic strategy. T-cells are regulated by different checkpoint proteins at the immunological synapse including the B7 ligands (B7-1 or CD80 and B7-2 or CD86), which is discussed in this review. These ligands are typically expressed on antigen presenting cells and interact with CD28 and cytotoxic T lymphocyte antigen-4 (CTLA-4) receptors on T-cells. Their interactions with CD28 trigger a costimulatory signal that potentiates T-cell activation, function and survival in response to cognate antigen. In addition, their interactions with CTLA-4 can also inhibit certain effector T-cell responses, particularly in response to sustained antigen stimulation. Through these mechanisms, the balance between T-cell activation and suppression is maintained, preventing the occurrence of immunopathology. Given their crucial roles in immune regulation, targeting B7 ligands has been an attractive strategy in cancer and autoimmunity. This review presents an overview of the essential roles of B7-1, highlighting the therapeutic benefits of modulating this protein in immunotherapy, and reviewing earlier and state-of-the-art efforts in developing anti-B7-1 inhibitors. Finally, we discuss the challenges facing the design of selective B7-1 inhibitors and present our perspectives for future developments.
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