What is Sipuleucel-T
Sipuleucel-T (trade name Provenge) is the first autologous cellular immunotherapy and this is the first immunotherapy for prostate cancer to receive FDA approval. Sipuleucel-T consists of autologous peripheral blood mononuclear cells (PBMCs), including antigen presenting cells, that have been activated with PAP-GM-CSF, a recombinant human protein. PAP-GM-CSF consists of prostatic acid phosphatase (PAP), an antigen expressed in prostate cancer tissue, linked to granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune cell activator.
Normally, the goal of immunotherapy is to stimulate the body’s natural defenses (such as the white blood cells called dendritic cells, T-lymphocytes and mononuclear cells) in a specific manner so that they attack and destroy, or at least prevent, the proliferation of cancer cells. Specificity is attained by intentionally exposing a patient’s white blood cells to a particular protein (called an antigen) associated with the prostate cancer. This exposure “trains” the white blood cells to target and attack the prostate cancer cells. Clinically, this is expected to result in a decrease in the size and/or number of cancer sites, an increase in the time to cancer progression, and/or an increase in survival of the patient.
Sipuleucel-T differs from other infused anti-cancer therapies. Most such anti-cancer therapies are manufactured and sold by a biopharmaceutical company and then purchased by and dispensed from a pharmacy. In contrast, once the decision is made to treat with sipuleucel-T, a multi-step process is used to produce sipuleucel-T. Sipuleucel-T is made individually for each patient with his own white blood cells. The patient’s white blood cells are removed via a procedure called leukapheresis. In a laboratory the white blood cells are exposed to PA2024, which is a molecule created by linking prostatic acid phosphatase (PAP) with granulocyte/macrophage-colony stimulating factor (GM-CSF). PAP is an antigen specifically associated with prostate cancer cells; GM-CSF is a protein that targets a receptor on the surface of white blood cells. Hence, PAP serves to externally manipulate the immunological functioning of the patient’s white blood cells while GM-CSF serves to stimulate the white blood cells into action. As noted in the FDA’s clinical review, each dose of sipuleucel-T contains a minimum of 40 million treated white blood cells, however there is “high inherent variability” in the yield of sipuleucel-T from leukapheresis to leukapheresis in the same patient as well as from patient to patient. The treated white blood cells are then infused back into the same patient.
The FDA-approved dosing regimen is three doses with each dose administered two weeks apart.
Also see Medicare coverage information for Provenge
