Sipuleucel-T
Sipuleucel -T, also called APC8015, is the name of an immune therapeutic agent which is to be used as a therapeutic cancer vaccine in the future for the treatment of prostate cancer. Sipuleucel - T consists of autologous ( autologous ) dendritic cells were incubated ex vivo with the fusion protein PA2024.
Sipuleucel -T was developed under the brand name Provenge by the U.S. company Dendreon and approved on 29 April 2010 after the completion of Phase III clinical trials by the FDA as a drug in the United States. The EU approval for 28 countries took place on 6 September 2013.
Description
Sipuleucel - T is to the immune system of patients who are already suffering from prostate cancer, stimulate in order to fight the tumor. These (Peripheral Blood Mononuclear Cell PBMC, engl. ) Be the patient by leukapheresis ( " blood washing " ) mononuclear cells of peripheral blood taken. By centrifugation, the cells are further enriched and incubated with the fusion protein PA2024 for 40 hours. The cells are then washed and resuspended in Ringer -lactate solution. The entire process takes about 48 hours. This suspension ( Sipuleucel -T) is then infused into the patient on an outpatient basis. The maximum stimulation of T cells is achieved after three infusions in two weeks.
The fusion protein PA2024 consists of the enzyme prostate- specific acid phosphatase (English prostatic acid phosphatase, PAP), which is (English granulocyte macrophage colony-stimulating factor ) associated with human glycoprotein GM -CSF. PAP is the tumor antigen. It is expressed by 95 percent of malignant prostate cells but not from healthy.
Induced T cells are directed against the PA2024 incubation with tumor antigen and are intended to combat the PAP in the body of the patient, the cells expressing this tumor antigen. Ideally, these are the cells of the primary tumor and its metastases.
Results of clinical trials
In a study of 127 patients with untreatable metastatisierten and hormone-refractory tumors, the median survival time increased from 21.4 months in the control group who received the placebo, 25.9 months for the group treated with Sipuleucel - T group. Progression-free survival was ( not significantly ) increased from 10 months to 11.7 months. The survival rate after three years increased from 11 to 34 percent. The competent authority in the United States for admission Food and Drug Administration (FDA ) refused but in 2007 first admission. The FDA decision was preceded by an advisory meeting. In it, 13 the consultant and 4 had voted against authorization. All 17 saw the drug to be safe. After the meeting, two of the consultants had explicitly expressed in written form to the FDA against the admission of Sipuleucel -T. This was ultimately the decisive factor in the FDA's approval first refused and another study requested.
In another phase III trial (IMPACT = Immunotherapy for Prostate Adeno Carcinoma Treatment ), which was a multicenter, double-blind, placebo- controlled carried out with over 500 patients, 2009, the following results were published: the median survival time was 4.1 months and the three- year survival rate increases to 38 percent.
A treatment cycle comprises three infusion of Sipuleucel -T. The costs for this are in the United States at $ 93 000 U.S..
Critics both the high cost of Sipuleucel -T, with an average of 23 000 U.S. $ per " recovered " month, as well as the design of the study. Thereby Sipuleucel -T was not compared with any other therapeutic agent, such as docetaxel, were tested. In this case, no significant increase of the median survival time had been detected may be.
Side effects
In the clinical studies, it was found that Sipuleucel -T is generally well tolerated by the patients. Common side effects are fever, tremor, and feeling cold. There were no indications of a possible autoimmune disease are found that could be triggered by an interaction of PAP tumor antigen with the normal tissue. This would in principle be possible, as PAP is not expressed by normal tissues.