Abagovomab
Encyclopedia
Abagovomab is a mouse
anti-idiotype
monoclonal antibody whose variable epitope mirrors a tumour antigen (CA-125
) highly expressed in the epithelial ovarian cancer
. Abagovomab does not bind directly to CA-125, but it works as a "surrogate" antigen, enabling the immune system to identify and attack tumour cells displaying the CA-125 protein. Through this, it is hoped that the body's immune system may be able to combat any remaining individual tumour cells and thus prevent recurrence of the disease.
The vaccine showed hardly any side effects in preliminary studies.
In spite of initially successful treatment with surgery and chemotherapy, which forces back the tumour "completely", i.e. into no longer visible residues, there is a relapse of the disease (recurrence) in more than half the women affected. Today, no further therapy would be conducted in this situation as long as the disease did not occur again, i.e. clinical monitoring of the symptom-free patients as part of follow-up care is the current standard procedure.
In this time-window of the patient’s history so called ‘watch and wait’ abagovomab is potentially capable of deferring or even preventing the occurrence of the relapse.
. A multicenter clinical trial, internationally known as MIMOSA (Monoclonal antibody Immunotherapy for Malignancies of the Ovary by Subcutaneous Abagovomab), in which Abagovomab will be administered as maintenance therapy (after first line therapy with surgery and chemotherapy), is ongoing in patients with ovarian cancer.
Nine hundred women in whom the ovarian tumour was removed by surgery and standard chemotherapy with paclitaxel
and carboplatin
can be enrolled in the MIMOSA study, involving eight countries throughout the world (Germany
, USA
, Italy
, Poland
, Czech Republic
, Spain
, Hungary
and Belgium
) in more than 120 experienced clinical sites.
Phase III of the trial showed no evidence of slowing ovarian cancer with a monoclonal antibody against CA125.
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
anti-idiotype
Idiotype
In immunology, an idiotype is a shared characteristic between a group of immunoglobulin or T cell receptor molecules based upon the antigen binding specificity and therefore structure of their variable region...
monoclonal antibody whose variable epitope mirrors a tumour antigen (CA-125
CA-125
CA-125 also known as mucin 16 or MUC16 is a protein that in humans is encoded by the MUC16 gene. MUC16 is a member of the mucin family glycoproteins...
) highly expressed in the epithelial ovarian cancer
Ovarian cancer
Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....
. Abagovomab does not bind directly to CA-125, but it works as a "surrogate" antigen, enabling the immune system to identify and attack tumour cells displaying the CA-125 protein. Through this, it is hoped that the body's immune system may be able to combat any remaining individual tumour cells and thus prevent recurrence of the disease.
Current status
Abagovomab is currently under clinical development in patients with advanced ovarian cancer, as consolidation of the remission status obtained following surgery and standard platinum and taxane first line chemotherapy.Phase II
In a Phase II study on 119 patients with advanced ovarian cancer in which the standard therapies had already been ineffective, treatment with abagovomab led to a prolongation of survival time (23.4 months compared to 4.9 months) in those patients who responded to the vaccination, i.e. those in whom the formation of antibodies against the tumour was proven (almost 70 % of patients).The vaccine showed hardly any side effects in preliminary studies.
Ovarian cancer
Ovarian cancer is the most malignant tumour of the female reproductive organs. After endometrial cancer, it is the second most common genital tumour in women with approximately 9,000 women newly affected each year and, because of its aggressiveness, it has the highest mortality rate. This is due in part to the fact that there is no screening examination for early detection, and that the disease is therefore usually only discovered at an advanced stage, and in part to the tumour's tendency, although responding well to initial treatment, to recur again later.In spite of initially successful treatment with surgery and chemotherapy, which forces back the tumour "completely", i.e. into no longer visible residues, there is a relapse of the disease (recurrence) in more than half the women affected. Today, no further therapy would be conducted in this situation as long as the disease did not occur again, i.e. clinical monitoring of the symptom-free patients as part of follow-up care is the current standard procedure.
In this time-window of the patient’s history so called ‘watch and wait’ abagovomab is potentially capable of deferring or even preventing the occurrence of the relapse.
Development
Abagovomab has been developed by the pharmaceutical company MenariniMenarini
The Menarini Group is an Italian pharmaceutical company. It was founded in Naples, Italy, in 1886, and has three divisions: Menarini Ricerche, Menarini Biotech and Menarini Diagnostics. It is committed to the search for pharmacological solutions for such therapeutic areas as cardiovascular...
. A multicenter clinical trial, internationally known as MIMOSA (Monoclonal antibody Immunotherapy for Malignancies of the Ovary by Subcutaneous Abagovomab), in which Abagovomab will be administered as maintenance therapy (after first line therapy with surgery and chemotherapy), is ongoing in patients with ovarian cancer.
Nine hundred women in whom the ovarian tumour was removed by surgery and standard chemotherapy with paclitaxel
Paclitaxel
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...
and carboplatin
Carboplatin
Carboplatin, or cis-Diammineplatinum is a chemotherapy drug used against some forms of cancer...
can be enrolled in the MIMOSA study, involving eight countries throughout the world (Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
, USA
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, Italy
Italy
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
, Poland
Poland
Poland , officially the Republic of Poland , is a country in Central Europe bordered by Germany to the west; the Czech Republic and Slovakia to the south; Ukraine, Belarus and Lithuania to the east; and the Baltic Sea and Kaliningrad Oblast, a Russian exclave, to the north...
, Czech Republic
Czech Republic
The Czech Republic is a landlocked country in Central Europe. The country is bordered by Poland to the northeast, Slovakia to the east, Austria to the south, and Germany to the west and northwest....
, Spain
Spain
Spain , officially the Kingdom of Spain languages]] under the European Charter for Regional or Minority Languages. In each of these, Spain's official name is as follows:;;;;;;), is a country and member state of the European Union located in southwestern Europe on the Iberian Peninsula...
, Hungary
Hungary
Hungary , officially the Republic of Hungary , is a landlocked country in Central Europe. It is situated in the Carpathian Basin and is bordered by Slovakia to the north, Ukraine and Romania to the east, Serbia and Croatia to the south, Slovenia to the southwest and Austria to the west. The...
and Belgium
Belgium
Belgium , officially the Kingdom of Belgium, is a federal state in Western Europe. It is a founding member of the European Union and hosts the EU's headquarters, and those of several other major international organisations such as NATO.Belgium is also a member of, or affiliated to, many...
) in more than 120 experienced clinical sites.
Phase III of the trial showed no evidence of slowing ovarian cancer with a monoclonal antibody against CA125.
Further reading
- Wagner U, Kohler S, Reinartz S, Giffels P, Huober J, Renke K, Schlebusch H, Biersack HJ, Mobus V, Kreienberg R, Bauknecht T, Krebs D, Wallwiener D. Immunological consolidation of ovarian carcinoma recurrences with monoclonal anti-idiotype antibody ACA125: immune responses and survival in palliative treatment. Clin Cancer Res. 2001;7(5):1154-62. http://clincancerres.aacrjournals.org/cgi/content/full/7/5/1154
- Reinartz S, Kohler S, Schlebusch H, Krista K, Giffels P, Renke K, Huober J, Mobus V, Kreienberg R, DuBois A, Sabbatini P, Wagner U. Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: immunological response and survival (phase Ib/II). Clin Cancer Res. 2004;10(5):1580-7. http://clincancerres.aacrjournals.org/cgi/content/full/10/5/1580
- Pfisterer J, du Bois A, Sehouli J, Loibl S, Reinartz S, Reuß A, Canzler U, Belau A, Jackisch C, Kimmig R, Wollschlaeger K, Heilmann V, Hilpert F. The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer. A phase I trial of the AGO-OVAR. Ann Oncol. 2006;17(10):1568-77. http://annonc.oxfordjournals.org/cgi/content/abstract/17/10/1568
- Sabbatini P, Dupont J, Aghajanian C, Derosa F, Poynor E, Anderson S, Hensley M, Livingston P, Iosonos A, Spriggs D, McGuire W, Reinartz S, Schneider S, Grande C, Lele S, Rodabaugh K, Kepner J, Ferrone S, Odunsi K. Phase I study of abagovomab in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Clin Cancer Res. 2006;12(18):5503-10. http://clincancerres.aacrjournals.org/cgi/content/abstract/12/18/5503