↓ Skip to main content

Nonclinical Efficacy and Safety of CX-2029, an Anti-CD71 Probody–Drug Conjugate

Overview of attention for article published in Molecular Cancer Therapeutics, June 2022
Altmetric Badge

About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (96th percentile)
  • High Attention Score compared to outputs of the same age and source (95th percentile)

Mentioned by

news
9 news outlets
twitter
2 tweeters
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Nonclinical Efficacy and Safety of CX-2029, an Anti-CD71 Probody–Drug Conjugate
Published in
Molecular Cancer Therapeutics, June 2022
DOI 10.1158/1535-7163.mct-21-0193
Pubmed ID
Authors

Shweta Singh, Laura Serwer, Amy DuPage, Kristi Elkins, Niharika Chauhan, Matthew Ravn, Fritz Buchanan, Leyu Wang, Michael Krimm, Ken Wong, Jason Sagert, Kimberly Tipton, Stephen J. Moore, Yuanhui Huang, Andrew Jang, Eric Ureno, Adam Miller, Sarah Patrick, Shanti Duvur, Shouchun Liu, Olga Vasiljeva, Yingchun Li, Tracy Henriques, Ilaria Badagnani, Shawn Jeffries, Siew Schleyer, Rob Leanna, Claus Krebber, Sridhar Viswanathan, Luc Desnoyers, Jonathan Terrett, Marcia Belvin, Susan Morgan-Lappe, W. Michael Kavanaugh, Jennifer Richardson

Abstract

Probody® therapeutics(Pb-Tx) are conditionally activated antibody-drug conjugates designed to remain inactive until proteolytically activated in the tumor microenvironment, enabling safer targeting of antigens expressed in both tumor and normal tissue. Previous attempts to target CD71, a highly expressed tumor antigen, have failed to establish an acceptable therapeutic window due to widespread normal tissue expression. This study evaluated whether a Probody-drug conjugate targeting CD71 can demonstrate a favorable efficacy and tolerability profile in preclinical studies for the treatment of cancer. CX-2029, a Pb-Tx conjugated to vcMMAE, was developed as a novel cancer therapeutic targeting CD71. Preclinical studies were performed to evaluate the efficacy and safety of this anti-CD71 PDC in mouse patient-derived xenograft(PDX) models and cynomolgus monkeys, respectively. CD71 expression was detected at high levels by IHC across a broad range of tumor and normal tissues. In vitro, the masked Pb-Tx form of the anti-CD71 PDC displayed >50-fold reduced affinity for binding to CD71 on cells compared with protease-activated, unmasked anti-CD71 PDC. Potent in vivo tumor growth inhibition (stasis or regression) was observed in >80% of PDX models(28/34) at 3 or 6mg/kg. Anti-CD71 PDC remained mostly masked(>80%) in circulation throughout dosing in cynomolgus monkeys at 2, 6, and 12mg/kg and displayed a 10-fold improvement in tolerability compared with an anti-CD71 ADC, which was lethal. Preclinically, anti-CD71 PDC exhibits a highly efficacious and acceptable safety profile that demonstrates the utility of the Pb-Tx platform to target CD71, an otherwise undruggable target. These data support further clinical development of the anti-CD71 PDC CX-2029 as a novel cancer therapeutic.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Attention Score in Context

This research output has an Altmetric Attention Score of 64. 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 12 August 2022.
All research outputs
#521,962
of 21,812,557 outputs
Outputs from Molecular Cancer Therapeutics
#56
of 3,781 outputs
Outputs of similar age
#12,378
of 338,438 outputs
Outputs of similar age from Molecular Cancer Therapeutics
#3
of 46 outputs
Altmetric has tracked 21,812,557 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,781 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.0. This one has done particularly well, scoring higher than 98% 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 338,438 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 46 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 95% of its contemporaries.