646 Safety of Leukapheresis in Prostate Cancer Patients Receiving Sipuleucel-T

Flanigan, Robert C.; Price, Thomas J.; Whitmore, James B.; Holman, Joan

doi:10.1016/j.juro.2011.02.1548

Cited by 4 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mononuclear cells removed during leukapheresis constitute only a small percentage of the body’s total pool of lymphocytes [22–24] and are rapidly replenished [25] such that median cell counts were within normal ranges 2, 10, and 22 weeks after the third leukapheresis procedure [26, 27]. The PBMCs are cultured with the recombinant PAP-GM-CSF fusion antigen (PA2024), which is processed by APCs and presented as PAP epitopes to PAP-specific T cells [18].…”

Section: Discussionmentioning

confidence: 99%

Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer

Sheikh

Petrylak

Kantoff

et al. 2012

Cancer Immunol Immunother

233

241

View full text Add to dashboard Cite

PurposeSipuleucel-T, the first FDA-approved autologous cellular immunotherapy for treatment of advanced prostate cancer, is manufactured by activating peripheral blood mononuclear cells, including antigen presenting cells (APCs), with a fusion protein containing prostatic acid phosphatase. Analysis of data from three phase 3 trials was performed to immunologically characterize this therapy during the course of the three doses, and to relate the immunological responses to overall survival (OS).MethodsSipuleucel-T product characteristics [APC numbers, APC activation (CD54 upregulation), and total nucleated cell (TNC) numbers] were assessed in three randomized, controlled phase 3 studies (N = 737). Antigen-specific cellular and humoral responses were assessed in a subset of subjects. The relationships between these parameters and OS were assessed.ResultsAPC activation occurred in the first dose preparation [6.2-fold, (4.65, 7.70); median (25th, 75th percentile)] and increased in the second [10.6-fold (7.83, 13.65)] and third [10.5-fold (7.89, 13.65)] dose preparations. Cytokines and chemokines associated with activated APCs were produced during the manufacture of each dose; T-cell activation-associated cytokines were detected in the second and third dose preparations. Antigen-specific T cells were detectable after administration of the first sipuleucel-T dose. Cumulative APC activation, APC number, and TNC number correlated with OS (P < 0.05). Antigen-specific immune responses were observed in 78.8 % of monitored subjects and their presence correlated with OS (P = 0.003).ConclusionSipuleucel-T broadly engages the immune system by activating APCs ex vivo and inducing long-lived immune responses in vivo. These data indicate antigen-specific immune activation as a mechanism by which sipuleucel-T prolongs OS.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-012-1317-2) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer

Sheikh

Petrylak

Kantoff

et al. 2012

Cancer Immunol Immunother

233

241

View full text Add to dashboard Cite

show abstract

“…These measures increase the potential for treatment success and ensure a more comfortable experience for the patient. Finally, patients should be reassured that leukapheresis does not adversely affect their immune system (Flanigan, Price, Whitmore, & Holman, 2011).…”

Section: Patient Education Needsmentioning

confidence: 99%

Optimizing the Efficiency and Quality of Sipuleucel-T Delivery in an Academic Institution

Davis¹,

Wood²,

Dill³

et al. 2015

CJON

View full text Add to dashboard Cite

show abstract

“…50 There is no evidence that leukapheresis resulted in immune-depletion: less than 1% of the patient's total pool of lymphocytes is removed during each leukapheresis procedure, 22 and the median values for white blood cells and absolute neutrophil, T cell, B cell, NK cell and monocyte counts were within normal ranges at week 6, approximately 2 weeks after the third infusion. 50,51 An integrated safety analysis of 4 randomized, doubleblind, controlled clinical trials (D9901, D9902A, IMPACT and PROTECT) demonstrated that the adverse events (AEs) observed with sipuleucel-T at a rate at least twice that of control were: chills (53.1%), pyrexia (31.3%), headache (18.1%), myalgia (11.8%), influenza-like illness (9.7%) and hyperhidrosis (5.0%). 50 These events generally occurred within 1 d of infusion, were mild or moderate in severity and resolved within 2 d. No latent AEs following sipuleucel-T therapy were observed, and there was no evidence of an increased incidence of autoimmune events or secondary malignancies.…”

Section: Clinical Developmentmentioning

confidence: 99%

An overview of sipuleucel-T: Autologous cellular immunotherapy for prostate cancer

Wesley

Whitmore

Trager

et al. 2012

Human Vaccines & Immunotherapeutics

Self Cite

View full text Add to dashboard Cite

Sipuleucel-T, the first autologous active cellular immunotherapy approved by the United States Food and Drug Administration, is designed to stimulate an immune response to prostate cancer. Sipuleucel-T is manufactured by culturing a patient's peripheral blood mononuclear cells (including antigen presenting cells) with a recombinant protein comprising a tumor-associated antigen (prostatic acid phosphatase) and granulocyte-macrophage colony stimulating factor. Treatment consists of 3 infusions at approximately 2-week intervals, resulting in a prime-boost pattern of immune activation, a robust antigen-specific cellular and humoral immune response, and, consequently, a survival benefit in subjects with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. Adverse events are generally mild to moderate and resolve within 2 d. Serious adverse events occur at a low rate. As the first autologous cellular immunotherapy to demonstrate a survival benefit, sipuleucel-T is a novel oncologic therapeutic that warrants the reassessment of the current prostate cancer treatment paradigm.

show abstract

646 Safety of Leukapheresis in Prostate Cancer Patients Receiving Sipuleucel-T

Cited by 4 publications

References 0 publications

Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer

Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer

Optimizing the Efficiency and Quality of Sipuleucel-T Delivery in an Academic Institution

An overview of sipuleucel-T: Autologous cellular immunotherapy for prostate cancer

Contact Info

Product

Resources

About