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Anti-Extra Domain B Splice Variant of Fibronectin Antibody–Drug Conjugate Eliminates Tumors with Enhanced Efficacy When Combined with Checkpoint Blockade

Overview of attention for article published in Molecular Cancer Therapeutics, July 2022
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (64th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (53rd percentile)

Mentioned by

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5 tweeters

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2 Mendeley
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Title
Anti-Extra Domain B Splice Variant of Fibronectin Antibody–Drug Conjugate Eliminates Tumors with Enhanced Efficacy When Combined with Checkpoint Blockade
Published in
Molecular Cancer Therapeutics, July 2022
DOI 10.1158/1535-7163.mct-22-0099
Pubmed ID
Authors

Andrea T. Hooper, Kimberly Marquette, Chao-Pei Betty Chang, Jonathon Golas, Sadhana Jain, My-Hanh Lam, Magali Guffroy, Mauricio Leal, Hadi Falahatpisheh, Divya Mathur, Ting Chen, Kerry Kelleher, Kiran Khandke, Elwira Muszynska, Frank Loganzo, Edward Rosfjord, Judy Lucas, Zhengyan Kan, Chakrapani Subramanyam, Christopher O'Donnell, Dario Neri, Hans-Peter Gerber, Chad May, Puja Sapra

Abstract

Extra domain B splice variant of fibronectin (EDB+FN) is an extracellular matrix protein (ECM) deposited by tumor associated fibroblasts, and is associated with tumor growth, angiogenesis and invasion. We hypothesized that EDB+FN is a safe and abundant target for therapeutic intervention with an antibody drug conjugate (ADC). We describe the generation, pharmacology, mechanism of action and safety profile of an ADC specific for EDB+FN (EDB-ADC). EDB+FN is broadly expressed in the stroma of pancreatic, non-small cell lung (NSCLC), breast, ovarian and head and neck cancers, while restricted in normal tissues. In patient derived xenograft (PDX), cell line xenograft (CLX), and mouse syngeneic tumor models, EDB-ADC, conjugated to auristatin Aur0101 through site-specific technology, demonstrated potent anti-tumor growth inhibition. Increased phospho-histone H3, a pharmacodynamic biomarker of response, was observed in tumor cells distal to the target site of tumor ECM after EDB-ADC treatment. EDB-ADC potentiated infiltration of immune cells, including CD3+ T lymphocytes into the tumor, providing rationale for the combination of EDB-ADC with immune checkpoint therapy. EDB-ADC and anti-PD-L1 combination in a syngeneic breast tumor model led to enhanced anti-tumor activity with sustained tumor regressions. In nonclinical safety studies in non-human primates, EDB-ADC had a well-tolerated safety profile without signs of either on-target toxicity or the off-target effects typically observed with ADCs that are conjugated through conventional conjugation methods. These data highlight the potential for EDB-ADC to specifically target the tumor microenvironment, provide robust therapeutic benefit against multiple tumor types and enhanced activity anti-tumor in combination with checkpoint blockade.

Twitter Demographics

The data shown below were collected from the profiles of 5 tweeters 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 2 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 2 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 1 50%
Student > Ph. D. Student 1 50%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 1 50%
Biochemistry, Genetics and Molecular Biology 1 50%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 30 September 2022.
All research outputs
#7,062,920
of 22,365,276 outputs
Outputs from Molecular Cancer Therapeutics
#1,590
of 3,844 outputs
Outputs of similar age
#119,050
of 342,234 outputs
Outputs of similar age from Molecular Cancer Therapeutics
#21
of 43 outputs
Altmetric has tracked 22,365,276 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 3,844 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.1. This one has gotten more attention than average, scoring higher than 57% of its peers.
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 342,234 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.
We're also able to compare this research output to 43 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.