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Clinical Development of Immune Checkpoint Inhibitors
#MMPMID26161407
Ito A
; Kondo S
; Tada K
; Kitano S
Biomed Res Int
2015[]; 2015
(?): 605478
PMID26161407
show ga
Recent progress in cancer immunotherapy has been remarkable. Most striking are
the clinical development and approval of immunomodulators, also known as immune
checkpoint inhibitors. These monoclonal antibodies (mAb) are directed to immune
checkpoint molecules, which are expressed on immune cells and mediate signals to
attenuate excessive immune reactions. Although mAbs targeting tumor associated
antigens, such as anti-CD20 mAb and anti-Her2 mAb, directly recognize tumor cells
and induce cell death, immune checkpoint inhibitors restore and augment the
antitumor immune activities of cytotoxic T cells by blocking immune checkpoint
molecules on T cells or their ligands on antigen presenting and tumor cells.
Based on preclinical data, many clinical trials have demonstrated the acceptable
safety profiles and efficacies of immune checkpoint inhibitors in a variety of
cancers. The first in class approved immune checkpoint inhibitor is ipilimumab,
an anti-CTLA-4 (cytotoxic T lymphocyte antigen-4) mAb. Two pivotal phase III
randomized controlled trials demonstrated a survival benefit in patients with
metastatic melanoma. In 2011, the US Food and Drug Administration (FDA) approved
ipilimumab for metastatic melanoma. Several clinical trials have since
investigated new agents, alone and in combination, for various cancers. In this
review, we discuss the current development status of and future challenges in
utilizing immune checkpoint inhibitors.
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