Abstract
Numerous research reports have witnessed dramatic advancements in cancer therapeutic approaches through immunotherapy. Blocking immunological checkpoint pathways (mechanisms employed by malignant cells to disguise themselves as normal human body components) has emerged as a viable strategy for developing anticancer immunity. Through the development of effective immune checkpoint inhibitors (ICIs) in multiple carcinomas, advances in cancer immunity have expedited a major breakthrough in cancer therapy. Blocking a variety of ICIs, such as PD-1 (programmed cell death-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) has improved the immune system’s efficacy in combating cancer cells. Recent studies also supported the fact that ICIs combined with other potent antitumor candidates, such as angiogenic agents, could be a solid promising chemopreventive therapeutic approach in improving the effectiveness of immune checkpoint inhibitors. Immune checkpoint blockade has aided antiangiogenesis by lowering vascular endothelial growth factor expression and alleviating hypoxia. Our review summarized recent advances and clinical improvements in immune checkpoint blocking tactics, including combinatorial treatment of immunogenic cell death (ICD) inducers with ICIs, which may aid future researchers in creating more effective cancer-fighting strategies.
Highlights
Introduction iationsThe recent era has witnessed enormous advancements in the oncology field by introducing the immunotherapy concept in cancer therapeutics
In 2011, ipilimumab was developed as the first immune checkpoint inhibitors (ICIs) that gained FDA approval after its successful trials in metastatic melanomas
Pembrolizumab has been recognized as the first ICI that has been approved for first-line treatment in several melanomas via inhibiting immune-cell suppression and deactivation [29]
Summary
CTLA-4 is an immune checkpoint protein that is expressed on Treg cells and T-anergic cells. In 2011, ipilimumab was developed as the first ICI (immune checkpoint inhibitor) that gained FDA approval after its successful trials in metastatic melanomas Ipilimumab is another human Ig (immunoglobulin) G1 mAb (monoclonal antibody) targeting CTLA-4 that sterically blocks the interaction of CTLA-4 with CD86 and CD80 on T cells or antigen-presenting cells to prevent the inhibitory potential of CTLA-4, thereby permitting the binding of CD28 to CD80/CD86 and leading to T cell activation. Ipilimumab has been approved for its use in combination with nivolumab (PD-1 inhibitor) for the treatment of unresectable (advanced) melanoma, RCC, and MSI-h (metastatic microsatellite in-stability high) or dMMR (mismatch repair-deficient) colorectal cancer [14] Another CTLA-4 inhibitor is Tremelimumab (human IgG2 mAb), having a similar course of action to ipilimumab, which blocks the interaction between CD28 and CTLA-4, thereby inhibiting CTLA-4 mediated inactivation of immune cells [15]. The ipilimumab inhibitor obtained approval for metastatic (unresectable) melanoma and surgery adjuvant for high-risk cancers (melanoma)
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