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Single dose denileukin diftitox does not enhance vaccine-induced T cell responses or effectively deplete Tregs in advanced melanoma: immune monitoring and clinical results of a randomized phase II…

Overview of attention for article published in Journal for Immunotherapy of Cancer, June 2016
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1 tweeter

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33 Mendeley
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Title
Single dose denileukin diftitox does not enhance vaccine-induced T cell responses or effectively deplete Tregs in advanced melanoma: immune monitoring and clinical results of a randomized phase II trial
Published in
Journal for Immunotherapy of Cancer, June 2016
DOI 10.1186/s40425-016-0140-2
Pubmed ID
Authors

Jason J. Luke, Yuanyuan Zha, Karen Matijevich, Thomas F. Gajewski

Abstract

Depletion of CD25(+) Tregs improves anti-tumor immunity in preclinical models. Denileukin diftitox is a recombinant fusion protein of human IL-2 and diptheria toxin fragment that also can kill CD25(+) T cells. Prior clinical trials of denileukin diftitox suggested reduction of FoxP3(+) Tregs and some clinical responses. To investigate the immunologic effects of denileukin difitox on vaccine-specific immune responses in melanoma, a randomized clinical trial of single dose denileukin diftitox prior to vaccination versus vaccination alone in subjects with HLA-A2(+) metastatic melanoma was performed. Treatment included randomization to a 4-peptide vaccine (Melan-A, gp100, MAGE3 and NA17 with GM-CSF emulsified in Montanide) alone or after single dose of denileukin diftitox (18 mcg/kg). Vaccine was given every 2 weeks for 3 doses and, absent clinical progression, continued every 2 weeks. Blood and tumor biopsies were obtained pretreatment and after 3 vaccinations for immunologic assessments. In 17 treated subjects there were no drug-related G3-4 adverse events. One partial response and 8 stable disease were observed in 9 subjects (4 DD: 5 vaccine only) with no impact of denileukin diftitox on time to progression. Total peripheral Tregs were not significantly altered, and in 1 patient biopsy intra-tumoral FoxP3 transcripts were not reduced following denileukin diftitox. ELISA for IL2R-α demonstrated no impact on outcomes by soluble CD25 level. Immune monitoring suggested the development of modest vaccine-specific CD8(+) T cell responses in the control group, however immunization efficacy was actually reduced in the denileukin diftitox group. Our results indicate that denileukin diftitox did not effectively deplete Tregs, augment T cell responses, or improve clinical activity in melanoma. Clinicaltrials.gov ID: NCT00515528; Registered August 9, 2007.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Australia 1 3%
Unknown 32 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 18%
Other 4 12%
Student > Master 4 12%
Student > Ph. D. Student 3 9%
Professor 2 6%
Other 5 15%
Unknown 9 27%
Readers by discipline Count As %
Medicine and Dentistry 9 27%
Immunology and Microbiology 4 12%
Psychology 2 6%
Agricultural and Biological Sciences 2 6%
Nursing and Health Professions 1 3%
Other 6 18%
Unknown 9 27%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 June 2016.
All research outputs
#4,164,034
of 7,936,934 outputs
Outputs from Journal for Immunotherapy of Cancer
#216
of 308 outputs
Outputs of similar age
#142,129
of 262,309 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#7
of 7 outputs
Altmetric has tracked 7,936,934 research outputs across all sources so far. This one is in the 27th percentile – i.e., 27% of other outputs scored the same or lower than it.
So far Altmetric has tracked 308 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 20.3. This one is in the 18th percentile – i.e., 18% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 262,309 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 7 others from the same source and published within six weeks on either side of this one.