Originally designed and produced by a small biotech company located in New Jersey, Sipuleucel-T is the first-ever therapeutic cancer vaccine designed for the treatment of advanced and metastatic prostate cancer. Sipuleucel-T is designed following these eight steps:9
- Step 1. It starts with a neoantigen found to be expressed at high levels in the majority of prostate cancer cells. The neoantigen is called “prostatic acid phosphate” or PAP. Neoantigens, by the way, refer to protein markers not integral to normal cells, hence neoantigens are deemed as “foreign” or “alien” by the host immune system. Once identified, the host immune system mounts an immune attack to eliminate neoantigens and associated entities. PAP is only found on prostate cancer cells but not on normal cells; it is an ideal target to alert the host immune system.
- Step 2. Next, a cytokine called granulocyte-macrophage colony-stimulating factor (GM–CSF) is chemically linked to the PAP chain to form a protein complex.
- Step 3. The protein complex is incubated with the precursor form of dendritic cells (DC) collected from prostate cancer patients, leading to GM-CSF binding to the corresponding protein receptor on the surface of DC. Since the DCs are from the patient’s own body, they are called autologous DCs.
- Step 4. The interaction from the above step activates precursor DC to become mature DC that subsequently engulfs the protein complex of PAP-GM-CSF.
- Step 5. The autologous DCs that harbor PAP, prostate cancer-specific biomarkers, are infused back to the patient.
- Step 6. Once infused back into the patient, the mature DC acts as an antigen presentation cell (APC) to cytotoxic T cells, also called Killer T cells. Through this interaction, Killer T cells recognize PAP that is specific for prostate cancer cells.
- Step 7. Relying on this important piece of immune “intelligence”, Killer T cells successfully locate prostate cancer cells that express PAP on the surface.
- Step 8. Once seized on the targets, Killer T cells unleash the fierce “1–2 punch” by secreting an enzyme called “perforin” to poke holes in prostate cancer cells to help the second enzyme called “granzyme B” to enter prostate cancer cells, trigger the activation of apoptosis (also called programmed cell death). Prostate cancer cells are, therefore, hunted down and destroyed.
The (abbreviated) process is illustrated in the image to the right.
Sipuleucel-T, which is marketed under the trade name PROVENGE, was approved by the FDA in 2010 and has been shown to reduce prostate cancer death by 22.5–41%.10,11 Due to the complex vaccine production and administration processes and the high price, there is a certain level of reluctance to prescribe Sipuleucel-T despite its high recommendations.
