The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies
Abstract
Despite extensive investigation over the past three decades, cancer immunotherapy has produced limited success, with few agents achieving approval by the Food and Drug Administration and even the most effective helping only a minority of patients, primarily with melanoma or renal cancer. In recent years, immune checkpoints that maintain physiologic self-tolerance have been implicated in the down-regulation of anti-tumor immunity. Efforts to restore latent anti-tumor immunity have focused on antibody-based interventions targeting CTL antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) on T lymphocytes and its principal ligand (PD-L1) on tumor cells. Ipilimumab, an antibody targeting CTLA-4, appears to restore tumor immunity at the priming phase, whereas anti-PD-1/PD-L1 antibodies restore immune function in the tumor microenvironment. Although ipilimumab can produce durable long-term responses in patients with advanced melanoma, it is associated with significant immune-related toxicities. By contrast, antibodies targeting either PD-1 or PD-L1 have produced significant anti-tumor activity with considerably less toxicity. Activity was seen in patients with melanoma and renal cancer, as well as those with non-small-cell lung, bladder and head and neck cancers, tumors not previously felt to be sensitive to immunotherapy. The tolerability of PD-1-pathway blockers and their unique mechanism of action have made them ideal backbones for combination regimen development. Combination approaches involving cytotoxic chemotherapy, anti-angiogenic agents, alternative immune-checkpoint inhibitors, immunostimulatory cytokines and cancer vaccines are currently under clinical investigation. Current efforts focus on registration trials of single agents and combinations in various diseases and disease settings and identifying predictive biomarkers of response.
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Cites
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Self-citationSafety and activity of anti-PD-L1 antibody in patients with advanced cancer
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Cited by
Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy
Alix-Panabières, C., & Pantel, K. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1483 · Cited by 1,394
Liquid biopsy and minimal residual disease - latest advances and implications for cure
Pantel, K., & Alix-Panabières, C. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0187-3 · Cited by 1,110
The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation
Bardhan, K., Anagnostou, T., & Boussiotis, V. A. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00550 · Cited by 606
Immunological landscape and immunotherapy of hepatocellular carcinoma
Prieto, J., Melero, I., & Sangro, B. (2015) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.173 · Cited by 566
Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons
Naimi, A., Mohammed, R. N., Raji, A., Chupradit, S., Yumashev, A. V., Suksatan, W., Shalaby, M. N., Thangavelu, L., Kamrava, S., Shomali, N., et al. (2022) · Cell Communication and Signaling · doi:10.1186/s12964-022-00854-y · Cited by 507
Metadata
- Authors
- Philips, G. K., & Atkins, M.
- Venue
- International Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-10-16
- Volume
- 27
- Issue
- 1
- Pages
- 39-46
- ISSN
- 0953-8178 (ISSN-L)
- 1460-2377
- OpenAlex
- W2118396147
- Cited by
- 335
- References
- 9
- FWCI
- 16.80
- Type
- journal article
- Language
- en
- Open access
- closed
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