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Administration of low-dose combination anti-CTLA4, anti-CD137, and anti-OX40 into murine tumor or proximal to the tumor draining lymph node induces systemic tumor regression

Overview of attention for article published in Cancer Immunology, Immunotherapy, September 2017
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1 tweeter
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1 Google+ user

Citations

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34 Mendeley
Title
Administration of low-dose combination anti-CTLA4, anti-CD137, and anti-OX40 into murine tumor or proximal to the tumor draining lymph node induces systemic tumor regression
Published in
Cancer Immunology, Immunotherapy, September 2017
DOI 10.1007/s00262-017-2059-y
Pubmed ID
Authors

Jonathan P. O. Hebb, Adriane R. Mosley, Felipe Vences-Catalán, Narendiran Rajasekaran, Anna Rosén, Peter Ellmark, Dean W. Felsher

Abstract

The delivery of immunomodulators directly into the tumor potentially harnesses the existing antigen, tumor-specific infiltrating lymphocytes, and antigen presenting cells. This can confer specificity and generate a potent systemic anti-tumor immune response with lower doses and less toxicity compared to systemic administration, in effect an in situ vaccine. Here, we test this concept using the novel combination of immunomodulators anti-CTLA4, -CD137, and -OX40. The triple combination administered intratumorally at low doses to one tumor of a dual tumor mouse model had dramatic local and systemic anti-tumor efficacy in lymphoma (A20) and solid tumor (MC38) models, consistent with an abscopal effect. The minimal effective dose was 10 μg each. The effect was dependent on CD8 T-cells. Intratumoral administration resulted in superior local and distant tumor control compared to systemic routes, supporting the in situ vaccine concept. In a single tumor A20 model, injection close to the tDLN resulted in similar efficacy as intratumoral and significantly better than targeting a non-tDLN, supporting the role of the tDLN as a viable immunotherapy target in addition to the tumor itself. Distribution studies confirmed expected concentration of antibodies in tumor and tDLN, in keeping with the anti-tumor results. Overall intratumoral or peri-tDLN administration of the novel combination of anti-CTLA4, anti-CD137, and anti-OX40, all agents in the clinic or clinical trials, demonstrates potent systemic anti-tumor effects. This immunotherapeutic combination is promising for future clinical development via both these safe and highly efficacious routes of administration.

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 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 34 100%

Demographic breakdown

Readers by professional status Count As %
Unspecified 10 29%
Researcher 9 26%
Student > Ph. D. Student 4 12%
Student > Bachelor 4 12%
Other 2 6%
Other 5 15%
Readers by discipline Count As %
Unspecified 12 35%
Immunology and Microbiology 7 21%
Biochemistry, Genetics and Molecular Biology 4 12%
Engineering 3 9%
Agricultural and Biological Sciences 3 9%
Other 5 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 21 November 2018.
All research outputs
#7,478,063
of 12,968,588 outputs
Outputs from Cancer Immunology, Immunotherapy
#1,339
of 1,851 outputs
Outputs of similar age
#132,385
of 269,743 outputs
Outputs of similar age from Cancer Immunology, Immunotherapy
#17
of 36 outputs
Altmetric has tracked 12,968,588 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,851 research outputs from this source. They receive a mean Attention Score of 4.6. This one is in the 25th percentile – i.e., 25% of its peers scored the same or lower than it.
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We're also able to compare this research output to 36 others from the same source and published within six weeks on either side of this one. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.