. 2015 Nov; 3(18):267.
doi: 10.3978/j.issn.2305-5839.2015.10.27.

Immune checkpoint inhibitors: therapeutic advances in melanoma

Ivan Márquez-Rodas 1 Pablo Cerezuela 1 Ainara Soria 1 Alfonso Berrocal 1 Aldo Riso 1 María González-Cao 1 Salvador Martín-Algarra 1 
  • PMID: 26605313
  •     76 References
  •     39 citations


In recent years, new strategies for treating melanoma have been introduced, improving the outlook for this challenging disease. One of the most important advances has been the development of immunotherapy. The better understanding of the role of the immunological system in tumor control has paved the way for strategies to enhance the immune response against cancer cells. Monoclonal antibodies (mAbs) against the immune checkpoints cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have demonstrated high activity in melanoma and other tumors. Ipilimumab, an anti CTLA-4 antibody, was the first drug of this class that was approved. Although the response rate with ipilimumab is low (less than 20% of patients have objective responses), 20% of patients have long survival, with similar results in the first and second line settings. Nivolumab and pembrolizumab, both anti PD-1 inhibitors, have been approved for the treatment of melanoma, with response rates of 40% and a demonstrated survival advantage in phase III trials. This has marked a new era in the treatment of metastatic melanoma and much research is now ongoing with other drugs targeting checkpoint inhibitors. In addition, the agonist of activating molecules on T cells and their combinations are being investigated. Herein we review the clinical development of checkpoint inhibitors and their approval for treatment of metastatic melanoma.

Keywords: Checkpoint inhibitors; immunotherapy; melanoma; programmed cell death protein 1 (PD-1).

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Cancers (Basel), 2020 Jul 18; 12(7). PMID: 32674474    Free PMC article.
Pembrolizumab-induced bullous pemphigoid.
Christina W Sun, Shoshana K Grossman, Abhishek Aphale, Sylvia Hsu.
JAAD Case Rep, 2019 Apr 23; 5(4). PMID: 31008169    Free PMC article.
Rational Combination of Parvovirus H1 With CTLA-4 and PD-1 Checkpoint Inhibitors Dampens the Tumor Induced Immune Silencing.
Katrin Goepfert, Christiane Dinsart, +2 authors, Markus Moehler.
Front Oncol, 2019 Jun 14; 9. PMID: 31192129    Free PMC article.
Research Status and Outlook of PD-1/PD-L1 Inhibitors for Cancer Therapy.
Leilei Ai, Jian Chen, +4 authors, Xiaochun Yang.
Drug Des Devel Ther, 2020 Sep 29; 14. PMID: 32982171    Free PMC article.
Characterization of a single chain variable fragment of nivolumab that targets PD-1 and blocks PD-L1 binding.
Jong Shin, Paul J Phelan, +2 authors, Peter A Bullock.
Protein Expr Purif, 2020 Sep 29; 177. PMID: 32987122    Free PMC article.
Monitoring checkpoint inhibitors: predictive biomarkers in immunotherapy.
Min Zhang, Jingwen Yang, +3 authors, Qijun Qian.
Front Med, 2019 Jan 27; 13(1). PMID: 30680606
Telomerase-Targeted Cancer Immunotherapy.
Eishiro Mizukoshi, Shuichi Kaneko.
Int J Mol Sci, 2019 Apr 25; 20(8). PMID: 31013796    Free PMC article.
Stepping From Modeling Cancer Plasticity to the Philosophy of Cancer.
Jean Clairambault.
Front Genet, 2020 Dec 18; 11. PMID: 33329717    Free PMC article.
Inhibition of post-surgery tumour recurrence via a hydrogel releasing CAR-T cells and anti-PDL1-conjugated platelets.
Quanyin Hu, Hongjun Li, +8 authors, Zhen Gu.
Nat Biomed Eng, 2021 Apr 28; 5(9). PMID: 33903744    Free PMC article.
Infiltration of Immune Competent Cells into Primary Tumors and Their Surrounding Connective Tissues in Xenograft and Syngeneic Mouse Models.
Marlon Metzen, Michael Bruns, Wolfgang Deppert, Udo Schumacher.
Int J Mol Sci, 2021 May 01; 22(8). PMID: 33921688    Free PMC article.
Immune checkpoint inhibitor related hypophysitis: diagnostic criteria and recovery patterns.
Ha Nguyen, Komal Shah, +13 authors, Ramona Dadu.
Endocr Relat Cancer, 2021 Apr 24; 28(7). PMID: 33890870    Free PMC article.
Case Report: Autoimmune Pemphigus Vulgaris in a Patient Treated With Cemiplimab for Multiple Locally Advanced Cutaneous Squamous Cell Carcinoma.
Rosalba Buquicchio, Valentina Mastrandrea, +3 authors, Raffaele Filotico.
Front Oncol, 2021 Sep 21; 11. PMID: 34540666    Free PMC article.
The Emerging Interplay Between Recirculating and Tissue-Resident Memory T Cells in Cancer Immunity: Lessons Learned From PD-1/PD-L1 Blockade Therapy and Remaining Gaps.
Silvia Gitto, Ambra Natalini, Fabrizio Antonangeli, Francesca Di Rosa.
Front Immunol, 2021 Dec 07; 12. PMID: 34867987    Free PMC article.
Vitiligo-specific soluble biomarkers as early indicators of response to immune checkpoint inhibitors in metastatic melanoma patients.
Maria Luigia Carbone, Gabriele Madonna, +10 authors, Cristina Maria Failla.
Sci Rep, 2022 Apr 02; 12(1). PMID: 35361879    Free PMC article.