Evidence map›Paper›PMID 25649018›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2015

Humoral Immune Response against Nontargeted Tumor Antigens after Treatment with Sipuleucel-T and Its Association with Improved Clinical Outcome.

Debraj GuhaThakurta, Nadeem A Sheikh, Li-Qun Fan, Harini Kandadi, T Craig Meagher, Simon J Hall, Philip W Kantoff, Celestia S Higano, Eric J Small, Thomas A Gardner and 7 more

Open access · greenAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 1 pooled it
7.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

94 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.

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  6. Randomized Phase II Trial of Sipuleucel-T with or without Radium-223 in Men with Bone-metastatic Castration-resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
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34 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 3 institutions in 1 country.

Debraj GuhaThakurtaDendreon Corporation, Seattle, Washington.
Nadeem A SheikhDendreon Corporation, Seattle, Washington.
Li-Qun FanDendreon Corporation, Seattle, Washington.
Harini KandadiDendreon Corporation, Seattle, Washington.
T Craig MeagherDendreon Corporation, Seattle, Washington.
Simon J HallMount Sinai School of Medicine, New York, New York.
Philip W KantoffDana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Celestia S HiganoUniversity of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, Washington.
Eric J SmallUniversity of California, San Francisco, San Francisco, California.
Thomas A GardnerIndiana University Simon Cancer Center, Indianapolis, Indiana.
Kate BaileyDendreon Corporation, Seattle, Washington.
Tuyen VuDendreon Corporation, Seattle, Washington.
Todd DeVriesDendreon Corporation, Seattle, Washington.
James B WhitmoreDendreon Corporation, Seattle, Washington.
Mark W FrohlichDendreon Corporation, Seattle, Washington.
James B TragerDendreon Corporation, Seattle, Washington. cdrake@jhmi.edu jtrager@dendreon.com.
Charles G DrakeJohns Hopkins University School of Medicine, the Brady Urological Institute, Baltimore, Maryland. cdrake@jhmi.edu jtrager@dendreon.com.
Harvard University · USIcahn School of Medicine at Mount Sinai · USUniversity of California, San Francisco · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
NCI NIH HHS P30 CA006973
6 · The paper itself

Abstract

purposeAntitumor activity of cancer immunotherapies may elicit immune responses to nontargeted (secondary) tumor antigens, or antigen spread. We evaluated humoral antigen spread after treatment with sipuleucel-T, an immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC), designed to target prostatic acid phosphatase (PAP; primary antigen). EXPERIMENTAL

designSerum samples from patients with mCRPC enrolled in the placebo-controlled phase III IMPACT study (evaluable n = 142) were used to assess humoral antigen spread after treatment with sipuleucel-T. Immunoglobulin G (IgG) responses to self-antigens (including tumor antigens) were surveyed using protein microarrays and confirmed using Luminex xMAP. IgG responses were subsequently validated in ProACT (n = 33), an independent phase II study of sipuleucel-T. Association of IgG responses with overall survival (OS) was assessed using multivariate Cox models adjusted for baseline prostate-specific antigen (PSA) and lactate dehydrogenase levels.

resultsIn patients from IMPACT and ProACT, levels of IgG against multiple secondary antigens, including PSA, KLK2/hK2, K-Ras, E-Ras, LGALS8/PCTA-1/galectin-8, and LGALS3/galectin-3, were elevated after treatment with sipuleucel-T (P < 0.01), but not control. IgG responses (≥ 2-fold elevation posttreatment) occurred in ≥ 25% of patients, appeared by 2 weeks after sipuleucel-T treatment, and persisted for up to 6 months. IgG responses to PSA and LGALS3 were associated with improved OS in sipuleucel-T-treated patients from IMPACT (P ≤ 0.05).

conclusionsSipuleucel-T induced humoral antigen spread in patients with mCRPC. IgG responses were associated with improved OS in IMPACT. The methods and results reported may identify pharmacodynamic biomarkers of clinical outcome after sipuleucel-T treatment, and help in clinical assessments of other cancer immunotherapies. See related commentary by Hellstrom and Hellstrom, p. 3581.

Indexed as

AgedAntigens, NeoplasmCancer VaccinesHumansImmunity, HumoralImmunoglobulin GImmunotherapyKaplan-Meier EstimateMaleMiddle AgedProstate-Specific AntigenProstatic Neoplasms, Castration-ResistantTissue ExtractsAntigens, NeoplasmCancer VaccinesImmunoglobulin GProstate-Specific Antigensipuleucel-TTissue Extracts

Identifiers

PMID25649018
PMCPMC4868054
OpenAlexW2080388405

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.