Immune modulation for cancer therapy

Immune modulation in cancer refers to a range of treatments aimed at harnessing a patient's immune system to achieve tumour control, stabilisation, and potential eradication of disease. A novel therapeutic drug class called immune checkpoint-blocking antibodies modulate T-cell pathways that reg...

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Bibliographic Details
Published in:British journal of cancer 2014-12, Vol.111 (12), p.2214-2219
Main Authors: NAIDOO, J, PAGE, D. B, WOLCHOK, J. D
Format: Article
Language:English
Subjects:
Antibodies
Antigens
Biological and medical sciences
Cancer therapies
Cell death
Cytotoxicity
Drug dosages
Humans
Immunoglobulins
Immunotherapy
Immunotherapy - methods
Ligands
Lymphocytes
Medical sciences
Melanoma
Metastasis
Minireview
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Neoplasms - immunology
Neoplasms - therapy
Peptides
Proteins
Tumor necrosis factor-TNF
Tumors
Vaccines
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Summary:Immune modulation in cancer refers to a range of treatments aimed at harnessing a patient's immune system to achieve tumour control, stabilisation, and potential eradication of disease. A novel therapeutic drug class called immune checkpoint-blocking antibodies modulate T-cell pathways that regulate T cells and have the potential to reinvigorate an antitumour immune response. Ipilimumab was the first FDA-approved immune checkpoint antibody licensed for the treatment of metastatic melanoma (MM) and blocks a checkpoint molecule called cytotoxic T-lymphocyte antigen 4 (CTLA-4). Herein we review the preclinical and clinical development of ipilimumab. We outline the mode of action of these agents and other immune checkpoint inhibitors, the management of their toxicities, and how to adequately assess response to treatment. As a result of these data, a number of other antibodies that block novel checkpoint molecules including programmed death-1 (PD-1), and corresponding ligands such as programmed death ligand-1 (PD-L1) are under preclinical and clinical development, and have demonstrated activity in multiple tumour types. This review will summarise the mechanism of action and clinical development of immune checkpoint antibodies, as well as lessons learned in the management and assessment of patients receiving these agents.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2014.348