Ipilimumab:
What is it?

Ipilimumab:
How is it Used?


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Ipilimumab Overview

Overview

Ipilimumab (sold as Yervoy) was approved for metastatic melanoma treatment by the FDA March 20111 and is a promising example of cancer immunotherapy. The drug is classified as a biotherapy, not a chemotherapy. Where chemotherapy kills dividing cells and biotherapy bolsters the body’s immune system to fight the disease. Ipilimumab was developed from research by Dr. James Allison in the 1990s2 to increase the body’s immune fight against cancer tumors by interfering with a mechanism tumors used to evade natural attack. By blocking the signals limiting immune response, the body is enabled to attack the tumors. The results of the Phase III trials showed that median overall survival was 10 months for patients treated using Yervoy, compared with six months for treatment using standard chemotherapy. Combined chemotherapy and Yervoy cancer immunotherapy showed average survival of 10 months. While the results are promising, they only benefitted 20-30% of the patients, and there were significant side effects. The best result was that 4 out of 403 lived 52-56 months.

How Ipilimumab Works

The normal body immune system attempts to kill foreign cells, but not the body’s own cells. Tumor cells are the body’s own cells, but the changes that lead to excessive growth make the cells slightly different. If that difference were identified, then the body’s immune system could kill those tumor cells. Normally CTLA-4 blocks the immune response and protects the body’s regular cells. Ipilimumab binds to the receptors on immune cells in place of the CTLA-4 and dials down the prevention of immune cells from killing the regular cells. The goal is for the immune system to now kill the tumor cells preferentially over the regular cells, which was observed for 20-30% of the patients. There is a difficult balance where the more powerful immune system does attack the body’s regular cells as well and leads to auto-immune disorder side effects like rashes and trouble with digestion. This is the main challenge of cancer immunotherapy. While Ipilimumab was tested and approved for metastatic melanoma, there are ongoing studies for lung, ovarian, and prostate cancer where it is suspected that the immune system would preferentially attack those cancerous cells too.

References

  1. "Ipilimumab." U S Food and Drug Administration Home Page. 25 Mar. 2011. Web. 02 Nov. 2011. <http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm248478.htm>.
  2. Peggs, KS, SA Quezada, AJ Korman, and JP Allison. "Principles and Use of Anti-CTLA4 Antibody in Human Cancer Immunotherapy." Current Opinion in Immunology(2006): 206-13. Http://www.ncbi.nlm.nih.gov. Pub Med, 18 Apr. 2006. Web. 04 Nov. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/16464564?dopt=Citation>.
  3. Wolchok, Jedd D., Jeffrey S. Weber, and Omid Hamid. "Ipilimumab Efficacy and Safety in Patients with Advanced Melanoma: a Retrospective Analysis of HLA Subtype from Four Trials." Cancer Immunology (2010). Print.
  4. Robert, C., L. Thomas, and I. Bondarenko. "Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma." New England Journal of Medicine 364.26 (2011): 2517-526. Print.
  5. "Dacarbazine, DTIC Dome, DIC - Chemotherapy Drugs, Chemo Drug Side Effects."Chemotherapy Drugs and Side Effects Information - Chemo Care. Web. 02 Nov. 2011. <http://www.chemocare.com/bio/dacarbazine.asp>.
  6. Jelic, S., N. Babovic, and V. Kovcin. "Comparison of the Efficacy of Two Different Dosage Dacarbazine-based Regimens and Two Regimens without Dacarbazine in Metastatic Melanoma: a Single-centre Randomized Four-arm Study." Melanoma Results. Pub Med, 12 Feb. 2002. Web. 02 Nov. 2011. <http://www.ncbi.nlm.nih.gov/pubmed/11828263>.
  7. Brockey, Mike. "I Am Now on Vemurafenib and Feeling Pretty Good." SMelanoma, Cancer Stinks! Blogger.com, 22 Aug. 2011. Web. 02 Nov. 2011. <http://www.smelanoma.com/2011/08/i-am-now-on-vemurafenib-and-feeling.html>.
  8. "Melanoma (stage III or IV) - Ipilimumab: Appraisal Consultation Document." Http://guidance.nice.org.uk. National Institute for Clinical Excellence, 14 Oct. 2011. Web. 04 Nov. 2011. <http://guidance.nice.org.uk/TA/WaveCRS2/48/Consultation/DraftGuidance>.
  9. "Yervoy (patient Information)." Www.yervoy.com. Bristol-Meyers Squibb. Web. 2 Nov. 2011. <http://www.yervoy.com/patient.aspx>

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