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    Can The Cancer Vaccine Sipuleucel-T Sip The Hell Out Of Cancers ?
    By Anirudha Lakshmin... | November 2nd 2010 06:10 AM | Print | E-mail | Track Comments
    About Anirudha

    Hello, I am a PhD graduate from molecular genetics laboratory, Indian Institute of Technology (IIT), Bombay. I am presently working for a Biotech...

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    Sipuleucel-T (Provenge) was the first therapeutic cancer vaccine to be approved by the FDA for Prostate cancers. Sipuleucel-T consists of Peripheral blood mononuclear cells (PBMCs) including Antigen presenting cells (APCs) was developed by Dendreon. The APCs that have been activated for a definite period in cell culture with recombinant protein containing Prostatic acid phosphatase (PAP) and Granuocyle macrophage colony stimulating factor (GM-CSF).

    PAP is expressed in 95% of prostate cancers. GM-CSF is an immune cell activator. The recombinant protein charges the APCs resulting in the expression of CD54 on its surface and is involved with T-cell interaction. Therefore, the active component of Sipuleucel-T contains APCs, T-Cells, B-cells and Natural Killer cells. However, the potency of Sipuleucel-T depends on the number of CD54+ cells.

    GM-CSF-PAP recombinant protein-> PBMCs ( APCs) in cell culture -> Activated APCs CD54+ -> APC CD54+ - T-Cell interactions -> Activated PBMCs trigger against PAP expressing Prostate cancer.

    Clinical trials with patients with Metastatic cancer showed promising results and subsequently the product was approved by the FDA for the treatment of asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer.

    The product is very similar to a conventional vaccine, the only difference being that here the activated cells themselves are injected instead of the antigen. This is a good start and will pave way for many to follow. 

    References:

    • Nature Reviews Drug Discovery 9, 513-514 (July 2010)
    • Higano CS, Schellhammer PF, Small EJ, et al. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009;115:3670-3679.
    • Small EJ, Schellhammer PF, Higano CS, et al. Placebo-controlled phase 3 trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006 Jul 1;24(19):3089-3094. PMID:16809734.
    • http://www.cancer.gov/cancertopics/druginfo/sipuleucel-T