Ipilimumab
| Ipilimumab | ||
|---|---|---|
| Identifier | ||
| External IDs |
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| Drug information | ||
| ATC code | L01 XC11 | |
| DrugBank | DB06186 | |
| Drug class | Monoclonal antibody | |
Ipilimumab (MDX-010; trade name Yervoy ) is a biotechnologically produced, fully human monoclonal antibody that is used in the treatment of melanoma , an aggressive form of skin cancer . The effect is directed against the protein CTLA-4 .
Approval and Marketing
In the European Union , Yervoy was approved by the European Commission in July 2011; in the USA, approval by the American health authority FDA was granted in March 2011. Yervoy is manufactured by Bristol-Myers Squibb .
Manufacturing
Ipilimumab is a fully humanized monoclonal antibody of the IgG1κ type, which consists of a total of 1324 amino acids . This antibody is produced in a cell line from Chinese hamster ovaries ( CHO cells ), a process also being developed in hybridoma cells .
Spectrum of activity
Ipilimumab is used in the treatment of malignant melanoma, an aggressive form of skin cancer. Cytotoxic T cells ( CTLs ) are able to recognize and destroy cancer cells through receptors on their surface , as these produce antigens on their surface that are recognized by the immune system and the cancer cells then eliminate. Dendritic cells, for example, are used to present antigens to T cells and thus trigger an immune response . At the same time, however, the immune response is controlled by certain receptors such. B. CTLA-4 (English. Cytotoxic T-Lymphocyte Antigen 4 ) on the T-cell, which competitive bindings with certain co-stimulating signals (e.g. B7) on antigen-presenting cells , is regulated and weakened to avoid an overreaction to prevent. This means that cancer cells can no longer be destroyed either. The monoclonal antibody ipilimumab intervenes in this cycle, weakens the inhibitory signal of CTLA-4 and therefore acts as an enhancer of T cell function . This leads to the activation of T cells, proliferation and the infiltration of lymphocytes into the tumor and thus the death of tumor cells. A phase III clinical study carried out in 2011 showed a significant increase in overall survival with the combined use of ipilimumab and the cytostatic drug dacarbazine compared to treatment with chemotherapy alone. The five-year survival rate of patients treated with dacarbazine and ipilimumab was 18.2%, compared to 8.8% in the control group.
Clinical application
Ipilimumab is available as a concentrate for infusions. 3 mg ipilimumab per kg body weight are administered as an infusion over a period of 90 minutes. Overall, ipilimumab is administered every three weeks, with the therapy being carried out with four doses .
Loss of appetite, diarrhea, rash and feelings of tiredness or weakness are cited as very common side effects .
In combination with nivolumab , ipilimumab is more effective than anti-PD1 monotherapy in some melanomas .
See also
- Nomenclature of monoclonal antibodies , convention for naming monoclonal antibodies
Web links
- Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for: Ipilimumab
- Commercial link: Study overview on ipilimumab
Individual evidence
- ↑ a b c d e f Assessment Report for Yervoy. (PDF) EMA, accessed on July 22, 2014 (English).
- ↑ a b Evan J. Lipson Charles G. Drake: Ipilimumab: an Anti-CTLA-4 Antibody for Metastatic Melanoma . In: Clin. Cancer Res . 17, No. 22, 2011, pp. 6958-62. doi : 10.1158 / 1078-0432.CCR-11-1595 .
- ^ Bristol-Myers Squibb Receives Positive Decision from the National Institute of Health and Clinical Excellence (NICE) for YERVOY® (ipilimumab). Bristol-Myers Squibb, accessed July 22, 2014 .
- ↑ a b YERVOY® Ipilimumab basic information for partners in the healthcare sector Status: December. (PDF) (No longer available online.) Bristol-Myers Squibb, archived from the original on July 28, 2014 ; Retrieved July 22, 2014 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.
- ↑ a b c d e f Summary of Product Characteristics. (PDF) EMA, accessed on July 22, 2014 (English).
- ↑ News in skin cancer therapy. Pharmaceutical Newspaper Online, accessed July 22, 2014 .
- ↑ Melanoma: Life Extension with Two New Drugs. (No longer available online.) Deutsches Ärzteblatt, Ärzte-Verlag GmbH, archived from the original on March 4, 2016 ; Retrieved July 23, 2014 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.
- ^ N Engl J Med. 2011 Jun 30; 364 (26): 2517-26. doi: 10.1056 / NEJMoa1104621 . Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH Jr, Gascon P. , Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen TT, Humphrey R, Hoos A, Wolchok JD.
- ^ J Clin Oncol. 2015 Apr 1; 33 (10): 1191-6. doi: 10.1200 / JCO.2014.56.6018 . Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial. Maio M, Grob JJ, Aamdal S, Bondarenko I, Robert C, Thomas L, Garbe C, Chiarion-Sileni V, Testori A, Chen TT, Tschaika M, Wolchok JD.
- ↑ Patrick Terheyden, Angela Krackhardt, Thomas Eigenler: System therapy of melanoma. Use of immune checkpoint inhibitors and inhibition of intracellular signal transduction. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f., (July 22) 2019, pp. 497-504, especially p. 503.
