Putting the Pieces Together: Completing the Mechanism of Action Jigsaw for Sipuleucel-T

Journal of the National Cancer Institute
Ravi A MadanJames L Gulley

Abstract

Sipuleucel-T is an autologous cellular immunotherapy that induces an immune response targeted against prostatic acid phosphatase (PAP) to treat asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. In the phase III IMPACT study, sipuleucel-T was associated with a statistically significantly increased overall survival (OS) (median = 4.1 months) vs placebo. Patients with baseline prostate-specific antigen levels in the lowest quartile (≤22.1 ng/mL) exhibited a 13-month improvement in OS with sipuleucel-T. Together, this led sipuleucel-T to be approved and recommended as first-line therapy in various guidelines for treatment of metastatic castration-resistant prostate cancer. This review discusses the varied findings about the mechanisms of action of sipuleucel-T, bringing them together to form a more coherent picture. These pieces include inducing a statistically significant increase in antigen-presenting cell activation; inducing a peripheral immune response specific to the target (PAP) and/or immunizing (PA2024) antigens; stimulating systemic cytotoxic T-lymphocyte activity; and mediating antigen spread (ie, increased antibody responses to secondary proteins in addition to PAP and PA2024). Each ...Continue Reading

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Citations

Jun 10, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christos E KyriakopoulosDouglas G McNeel
Jan 13, 2021·Current Treatment Options in Oncology·Risa L Wong, Evan Y Yu
Apr 7, 2021·Prostate Cancer and Prostatic Diseases·Jacob Stultz, Lawrence Fong

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Methods Mentioned

BETA
leukapheresis
enzyme-linked immunosorbent
biopsies
biopsy

Clinical Trials Mentioned

NCT01133704
NCT03686683
NCT02463799
NCT01818986
NCT01804465
NCT03329742
NCT01833208
NCT01706458
NCT02036918
NCT02456571

Software Mentioned

STAND
STAMP
IMPACT

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