2010 New Drug Approvals - part IX - Sipuleucel-T (Provenge)

On April 29th, the FDA approved Sipuleucel-T (Tradename: Provenge, REsearch Code: APC-8015) a highly novel treatment (a cell-based vaccine) for hormone refractory (castration resistant) prostate cancer. Patients with this form of late-stage prostate cancer have refractory metastases after hormonal therapy even though they may have few symptoms. Sipuleucel-T has had a complex development and approval history (as a google search will readily show). Sipuleucel-T is a mixture of white blood cells that are extracted from the patient through a process called Leukapheresis, which is routinely used to isolate white blood cells e.g. for diagnostic purposes. In the 3 days that pass between the extraction of the white blood cells from the patient and the treatment with sipuleucel-T, the mixture is activated by exposing the extracted cells to an engineered protein called PAP-GM-CSF. In this, PAP stands for prostatic acid phosphatase (Uniprot P15309), which is produced in high amounts by metastasized prostate carcinoma cells. Among the cells extracted from the patient are antigen presenting cells which internalize the protein and, after lysosomal processing, present fragments of the proteins in conjunction with the immune stimulatory MHC class II molecules. This complex has an activating effect on all immune cells that have been in contact with PAP. Thus, upon re-infusion, the autologous immune cells promote a clonal growth of immune cells that are specifically active against the PAP-antigen and coordinate an immune response against the tumor cells, which present PAP antigen in abundance. In clinical trials with 512 patients, sipuleucel-T treatment increased patient survival by 4.1 months on average compared to no treatment. Among reported averse side effect are chills, nausea, fatigue and pain. Sipuleucel-T is marketed by Dendreon under the name Provenge. The full prescribing information for sipuleucel-T can be found here.

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