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2016 ; 9
(ä): 1767-76
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Tremelimumab: research and clinical development
#MMPMID27042127
Comin-Anduix B
; Escuin-Ordinas H
; Ibarrondo FJ
Onco Targets Ther
2016[]; 9
(ä): 1767-76
PMID27042127
show ga
The immune checkpoint therapy is a relatively recent strategy that aims to tweak
the immune system to effectively attack cancer cells. The understanding of the
immune responses and their regulation at the intracellular level and the
development of fully humanized monoclonal antibodies are the pillars of an
approach that could elicit durable clinical responses and even remission in some
patients with cancer. Most of the immune checkpoints that regulate the T-cell
responses (activation and inhibition) operate through proteins present on the
cytoplasmic membrane of the immune cells. Therefore, specific antibodies capable
of blocking the inhibitory signals should lead to unrestrained immune responses
that supersede the inhibitory mechanisms, which are naturally present in the
tumor microenviroment. The best-known and most successful targets for immune
checkpoint therapy are the cytotoxic T-lymphocyte antigen-4 and programmed cell
death-1 coreceptors. Tremelimumab (CP-675,206) is a fully humanized monoclonal
antibody specific for cytotoxic T-lymphocyte antigen-4, which has been
successfully used to treat patients with metastatic melanoma and some other
cancers. Although still a work in progress, the use of tremelimumab as an immune
checkpoint therapeutic agent is a promising approach alone or in combination with
other anticancer drugs. Here, we review the use of this antibody in a number of
clinical trials against solid tumors.
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