Sipuleucel-T: A Vaccine for Metastatic, Asymptomatic, Androgen-Independent Prostate Cancer

Patel, Punam H; Kockler, Denise R

doi:10.1345/aph.1k429

Cited by 66 publications

(46 citation statements)

References 15 publications

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“…Antigen-presenting cells (APCs), including dendritic cells, are activated by exposure to a prostatic acid phosphatase (PAP)-GM-CSF fusion protein in vitro. The activated cellular product is then reinfused into the same patient in three biweekly doses, with the goal of initiating a dynamic immune response targeting PAP, within the context of class I major histocompatibility complex, on the surface of prostate cancer cells [10,11]. It is important to note that the therapeutic cancer vaccines discussed in this review differ from traditional preventive vaccines (e.g., for infectious diseases) in that the primary goal of therapeutic cancer vaccines is not to prevent disease but rather to generate an active immune response against an existing malignancy.…”

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confidence: 99%

Therapeutic Cancer Vaccines in Prostate Cancer: The Paradox of Improved Survival Without Changes in Time to Progression

et al. 2010

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Therapeutic cancer vaccines represent a new class of agents in the treatment of cancer. Sipuleucel-T is an antigen-presenting cell-based vaccine that recently demonstrated a significant 4.8-month improvement in overall survival in advanced prostate cancer patients and was well tolerated. The findings of that study have been met with skepticism, primarily because the agent did not change initial disease progression and yet led to longer survival. Although the commonly accepted treatment paradigm suggests that treatments should initially decrease tumor volume, perhaps vaccines work differently. Vaccines may induce delayed responses not seen in the first few months of therapy or they may initiate a dynamic immune response that ultimately slows the tumor growth rate, resulting in longer survival. Subsequent therapies may also combine with the induced immune response, resulting in a combination that is more effective than conventional treatments alone. Also, other treatments may alter tumor-associated antigen expression, enhancing the immune response. Future trials are currently planned to investigate these hypotheses; however, the results of the sipuleucel-T vaccine in prostate cancer should not be dismissed. Results with another vaccine in prostate cancer are similar, perhaps suggesting a class effect. In a broader context, clinicians may need to reconsider how they measure success. Several agents have been approved that produce superior disease progression results, but do not affect overall survival. Given the toxicity and costs of cancer therapies, perhaps studies should put more weight on long-term survival endpoints than on short-term endpoints that may be less consequential. CURRENT APPROACHES TO TREATING PROSTATE CANCERSix years after the U.S. Food and Drug Administration (FDA) approved the use of docetaxel for the treatment of prostate cancer, a therapeutic cancer vaccine has demonstrated improved survival times in a large randomized, phase III trial in metastatic castration-resistant prostate cancer (CRPC) patients. Although this was, in fact, the second trial of this agent to show superior survival results in CRPC patients, data from the phase III trial of the sipuleucel-T vaccine (Provenge; Dendreon Corp., Seattle, WA) have raised many questions [1].Of the most prevalent solid tumor malignancies (lung, colon, breast, and prostate), prostate cancer has the fewest therapeutic options for patients with advanced disease. In fact, until earlier this year, only one chemotherapeutic regimen had been shown to confer a survival benefit for the nearly 200,000 men who will be diagnosed with prostate cancer in 2010 and the Ͼ27,000 who will succumb to the disease [2]. The regimen of docetaxel and prednisone was sanctioned by the FDA in 2004 for the treatment of metastatic CRPC based on longer survival time, by approximately 3 months [3,4]. In spite of the obvious need for additional treatments and promising preliminary studies, most subsequent clinical trials in metastatic CRPC patients have fallen short of c...

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confidence: 99%

Therapeutic Cancer Vaccines in Prostate Cancer: The Paradox of Improved Survival Without Changes in Time to Progression

et al. 2010

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“…These cells, which are enriched for antigen-presenting cells (APCs), are subsequently incubated with a recombinant fusion protein consisting of prostatic acid phosphatase (PAP) and granulocyte macrophage colony-stimulating factor (GM-CSF) (12,13). This process results in the activation of APCs and the final product is administered back to the patient by intravenous infusion.…”

Section: Cancer Vaccinesmentioning

confidence: 99%

Immunobiology and immunotherapy in genitourinary malignancies

Tsiatas

Grivas

2016

Ann. Transl. Med.

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“…Interest in DC vaccines has grown recently with the Food and Drug Administration's approval of sipuleucel-T (Provenge; Dendreon, Seattle, WA) [84], a therapeutic vaccine consisting of autologous DCs that have been loaded with a prostatic acid phosphatase (PAP)-GM-CSF fusion protein ex vivo for metastatic, androgen independent prostate cancer [85].…”

Section: Dendritic Cells and Immune-based Therapiesmentioning

confidence: 99%