Clinical Development of Immune Checkpoint Inhibitors

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...

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Bibliographic Details
Published in:BioMed research international 2015-01, Vol.2015 (2015), p.1-12
Main Authors: Kitano, Shigehisa, Tada, Kohei, Kondo, Shunsuke, Ito, Ayumu
Format: Article
Language:English
Subjects:
Apoptosis
Biomarkers
Biomarkers, Tumor - metabolism
Cancer
Cancer therapies
Care and treatment
Chemotherapy
Clinical trials
CTLA-4 Antigen - immunology
Drug Therapy, Combination
Gene expression
Homeostasis
Humans
Immune response
Immunotherapy
Immunotherapy - adverse effects
Ligands
Lymphocytes
Melanoma
Metastasis
Methods
Neoplasms - immunology
Neoplasms - therapy
Observations
Oncology
Pharmaceutical industry
Programmed Cell Death 1 Receptor - immunology
Prostate cancer
Review
T cell receptors
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Summary: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.
ISSN:2314-6133
2314-6141
DOI:10.1155/2015/605478