Home LiteratureArticle Details
PMID: 26047524 Published · ppublish English Journal Article Review

PD-1/PD-L1 inhibitors.

Current opinion in pharmacology ·Vol. 23 ·2015-08-00 ·Pages 32-8

Sunshine J, Taube JM

Abstract

Tumors may adopt normal physiologic checkpoints for immunomodulation leading to an imbalance between tumor growth and host surveillance. Antibodies targeting the PD-1/PD-L1 checkpoint have shown dynamic and durable tumor regressions, suggesting a rebalancing of the host-tumor interaction. Nivolumab and pembrolizumab are the anti-PD-1 antibodies that are currently the furthest in clinical development, and anti-PD-L1 agents under investigation include MPDL3280A, MEDI4736, and BMS-936559. These agents have been used to treat advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancer and Hodgkin lymphoma, amongst other tumor types. In this article, we review the updated response results for early clinical trials, note recent FDA actions regarding this class of agents, and summarize results across trials looking at PD-L1 status as a predictor of response to anti-PD-1/PD-L1.

MeSH Terms
Animals Antibodies, Monoclonal/pharmacology,therapeutic use Antineoplastic Agents/pharmacology,therapeutic use B7-H1 Antigen/antagonists & inhibitors,immunology Humans Neoplasms/drug therapy,immunology Programmed Cell Death 1 Receptor/antagonists & inhibitors,immunology
Chemicals
Antibodies, Monoclonal Antineoplastic Agents B7-H1 Antigen CD274 protein, human PDCD1 protein, human Programmed Cell Death 1 Receptor
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sunshine Joel
Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Taube Janis M
Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA; Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address: [email protected].
References (28)
28 references, click to expand
  1. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma.
    N Engl J Med. 2013 Jul 11;369(2):134-44 PMID: 23724846
  2. Nivolumab plus ipilimumab in advanced melanoma.
    N Engl J Med. 2013 Jul 11;369(2):122-33 PMID: 23724867
  3. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion.
    Nat Med. 2002 Aug;8(8):793-800 PMID: 12091876
  4. Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues.
    Immunol Lett. 2002 Oct 21;84(1):57-62 PMID: 12161284
  5. Expression of programmed death 1 ligands by murine T cells and APC.
    J Immunol. 2002 Nov 15;169(10):5538-45 PMID: 12421930
  6. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes.
    Int Immunol. 1996 May;8(5):765-72 PMID: 8671665
  7. Tumor-expressed B7-H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinoma.
    Clin Cancer Res. 2009 Oct 15;15(20):6341-7 PMID: 19825956
  8. Costimulator B7-DC attenuates strong Th2 responses induced by Nippostrongylus brasiliensis.
    J Immunol. 2010 Feb 15;184(4):2086-94 PMID: 20065112
  9. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates.
    J Clin Oncol. 2010 Jul 1;28(19):3167-75 PMID: 20516446
  10. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape.
    Sci Transl Med. 2012 Mar 28;4(127):127ra37 PMID: 22461641
  11. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
    N Engl J Med. 2012 Jun 28;366(26):2443-54 PMID: 22658127
  12. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer.
    N Engl J Med. 2012 Jun 28;366(26):2455-65 PMID: 22658128
  13. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer--response.
    Clin Cancer Res. 2013 Oct 1;19(19):5542 PMID: 24048329
  14. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma.
    J Clin Oncol. 2013 Dec 1;31(34):4311-8 PMID: 24145345
  15. Mitigating the toxic effects of anticancer immunotherapy.
    Nat Rev Clin Oncol. 2014 Feb;11(2):91-9 PMID: 24445516
  16. PD-L1 expression in the Merkel cell carcinoma microenvironment: association with inflammation, Merkel cell polyomavirus and overall survival.
    Cancer Immunol Res. 2013 Jul;1(1):54-63 PMID: 24416729
  17. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial.
    Lancet. 2014 Sep 20;384(9948):1109-17 PMID: 25034862
  18. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy.
    Clin Cancer Res. 2014 Oct 1;20(19):5064-74 PMID: 24714771
  19. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer.
    Nature. 2014 Nov 27;515(7528):558-62 PMID: 25428503
  20. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients.
    Nature. 2014 Nov 27;515(7528):563-7 PMID: 25428504
  21. PD-1 blockade induces responses by inhibiting adaptive immune resistance.
    Nature. 2014 Nov 27;515(7528):568-71 PMID: 25428505
  22. Nivolumab in previously untreated melanoma without BRAF mutation.
    N Engl J Med. 2015 Jan 22;372(4):320-30 PMID: 25399552
  23. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma.
    N Engl J Med. 2015 Jan 22;372(4):311-9 PMID: 25482239
  24. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer.
    Science. 2015 Apr 3;348(6230):124-8 PMID: 25765070
  25. B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells.
    J Exp Med. 2001 Apr 2;193(7):839-46 PMID: 11283156
  26. Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial.
    J Clin Oncol. 2015 May 1;33(13):1430-7 PMID: 25452452
  27. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial.
    Lancet Oncol. 2015 Apr;16(4):375-84 PMID: 25795410
  28. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada.
    J Natl Cancer Inst. 2000 Feb 2;92(3):205-16 PMID: 10655437
Article Info
Journal
Current opinion in pharmacology
Abbr.
Curr Opin Pharmacol
ISSN
1471-4973
Published
2015-08-00
Epub
2015-00-02
Pages
32-8
Language
English
Region
England
NLM ID
100966133
PMCID
PMC4516625
Subset
IM
Grants
NCI NIH HHS · R01 CA142779 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]