Ipilimumab

Ipilimumab
Fab fragment of ipilimumab (blue) binding CTLA-4 (green). From PDB entry 5TRU.
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetCTLA-4
Clinical data
Pronunciationi pi lim′ ue mab
Trade namesYervoy
Other namesBMS-734016,[1] MDX-010,[2] MDX-101
AHFS/Drugs.comMonograph
MedlinePlusa611023
License data
Pregnancy
category
  • AU: C
Routes of
administration		Intravenous (IV)
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life15 days[7]
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC6742H9972N1732O2004S40
Molar mass148634.46 g·mol−1
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Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.

Cytotoxic T lymphocytes (CTLs) can recognize and destroy cancer cells. However, an inhibitory mechanism interrupts this destruction.[8] Ipilimumab turns off this inhibitory mechanism and boosts the body's immune response against cancer cells.[8][9]

Ipilimumab was approved by the US Food and Drug Administration (FDA) in March 2011, for the treatment of melanoma, renal cell carcinoma (RCC), colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer (NSCLC), malignant pleural mesothelioma, esophageal cancer.[10][11][12][13] It is undergoing[when?] clinical trials for the treatment of bladder cancer[14] and metastatic hormone-refractory prostate cancer.[15]

The concept of using anti-CTLA4 antibodies to treat cancer was first developed by James P. Allison while he was director of the Cancer Research Laboratory at the University of California, Berkeley.[16][17] Clinical development of anti-CTLA4 was initiated by Medarex, which was later acquired by Bristol-Myers Squibb. For his work in developing ipilimumab, Allison was awarded the Lasker Award in 2015.[18] Allison later was the co-winner of the 2018 Nobel Prize in Physiology or Medicine.[19]

  1. ^ "Yervoy, ipilimumab (BMS-734016) - Product Profile - BioCentury". BioCentury Online Intelligence. BioCentury Publications. Retrieved 11 August 2016.
  2. ^ USAN. "STATEMENT ON A NONPROPRIETARY NAME ADOPTED BY THE USAN COUNCIL - ipilimumab" (Press release). American Medical Association (AMA). Archived from the original on 2016-02-23. Retrieved 2013-01-12.
  3. ^ "Regulatory Decision Summary for Yervoy". Drug and Health Products Portal. 7 December 2023. Retrieved 2 April 2024.
  4. ^ "Yervoy 5 mg/ml concentrate for solution for infusion - Summary of Product Characteristics (SmPC)". (emc). 3 August 2020. Retrieved 2 October 2020.
  5. ^ "Yervoy- ipilimumab injection". DailyMed. 13 August 2020. Retrieved 2 October 2020.
  6. ^ "Yervoy EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 2 October 2020.
  7. ^ "Ipilimumab: Uses, Interactions, Mechanism of Action". DrugBank Online. 25 March 2011. Retrieved 18 September 2024.
  8. ^ a b Syn NL, Teng MW, Mok TS, Soo RA (December 2017). "De-novo and acquired resistance to immune checkpoint targeting". The Lancet. Oncology. 18 (12): e731–e741. doi:10.1016/s1470-2045(17)30607-1. PMID 29208439.
  9. ^ Cite error: The named reference Ribas was invoked but never defined (see the help page).
  10. ^ "Yervoy". Opdivo. Bristol Myers Squibb. Retrieved 7 February 2024.
  11. ^ "Drug Approval Package: Yervoy (ipilimumab) Injection NDA #125377". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 2 October 2020.
  12. ^ Lacroix M (2014). Targeted Therapies in Cancer. Hauppauge, NY: Nova Sciences Publishers. ISBN 978-1-63321-687-7. Archived from the original on 2015-06-26. Retrieved 2014-07-13.
  13. ^ Pollack A (May 29, 2015). "New Class of Drugs Shows More Promise in Treating Cancer". New York Times. Retrieved May 30, 2015.
  14. ^ Clinical trial number NCT01524991 for "First-Line Gemcitabine, Cisplatin + Ipilimumab for Metastatic Urothelial Carcinoma" at ClinicalTrials.gov (completed)
  15. ^ Clinical trial number NCT00323882 for "Phase I/II Study of MDX-010 in Patients With Metastatic Hormone-Refractory Prostate Cancer (MDX010-21)" at ClinicalTrials.gov (completed)
  16. ^ Leach DR, Krummel MF, Allison JP (March 1996). "Enhancement of antitumor immunity by CTLA-4 blockade". Science. 271 (5256): 1734–1736. Bibcode:1996Sci...271.1734L. doi:10.1126/science.271.5256.1734. PMID 8596936. S2CID 7215817.
  17. ^ "UC Berkeley Cancer Research Lab » The Story of Yervoy (Ipilimumab)". crl.berkeley.edu.
  18. ^ Lasker Foundation. "Deep brain stimulation for Parkinson's disease". The Lasker Foundation.
  19. ^ "The Nobel Prize in Physiology or Medicine 2018 to James P. Allison and Tasuku Honjo". Archived from the original on 2018-12-24. Retrieved 2018-10-01.