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Rationale for targeting the immune system through checkpoint molecule blockade in the treatment of non-small-cell lung cancer.
- Source :
-
Annals of oncology : official journal of the European Society for Medical Oncology [Ann Oncol] 2013 May; Vol. 24 (5), pp. 1170-9. Date of Electronic Publication: 2013 Feb 07. - Publication Year :
- 2013
-
Abstract
- Background: Treatments of non-small-cell lung cancer (NSCLC)-particularly of the squamous subtype-are limited. In this article, we describe the immunomodulatory environment in NSCLC and the potential for therapeutic targeting of the immune system through cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 (PD-1) immune-checkpoint pathway blockade.<br />Materials and Methods: We searched PubMed and presented abstracts for publications describing the clinical benefit of checkpoint blockade in NSCLC.<br />Results: Antibody-mediated checkpoint molecule blockade is being investigated in NSCLC, and of these approaches, the anti-CTLA-4 antibody ipilimumab has undergone the most extensive clinical study. By targeting the immune system rather than specific antigens, checkpoint blockade agents differ from vaccine therapy. In a phase II study in advanced NSCLC, phased ipilimumab with chemotherapy demonstrated the greatest efficacy in squamous NSCLC. A phase I study of nivolumab, an anti-PD-1 antibody, has suggested that this agent is also active against squamous and non-squamous NSCLC. Ongoing phase III studies are evaluating the therapeutic potential of these agents.<br />Conclusions: Although treatment options for NSCLC are limited, a better understanding of the immune profile of this disease has facilitated the development of immunotherapeutics that target checkpoint blockade molecules, and clinical evaluation to date supports combining checkpoint blockade with chemotherapy for squamous NSCLC.
- Subjects :
- CTLA-4 Antigen immunology
Carcinoma, Non-Small-Cell Lung immunology
Humans
Immunomodulation
Ipilimumab
Lung Neoplasms immunology
Programmed Cell Death 1 Receptor immunology
Antibodies, Monoclonal therapeutic use
Antineoplastic Agents therapeutic use
CTLA-4 Antigen antagonists & inhibitors
Carcinoma, Non-Small-Cell Lung drug therapy
Lung Neoplasms drug therapy
Programmed Cell Death 1 Receptor antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1569-8041
- Volume :
- 24
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Annals of oncology : official journal of the European Society for Medical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 23393121
- Full Text :
- https://doi.org/10.1093/annonc/mds647