Human kallikrein peptidase 2 (hK2) is a prostate specific enzyme whose expression is governed by the androgen receptor (AR). AR is the central oncogenic driver of prostate cancer (PCa) and is also a key regulator of DNA repair in cancer. We report an innovative therapeutic strategy that exploits the hormone-DNA repair circuit to enable molecularly-specific alpha particle irradiation of PCa. Alpha-particle irradiation of PCa is prompted by molecularly specific-targeting and internalization of the humanized monoclonal antibody hu11B6 targeting hK2 and further accelerated by inherent DNA-repair that up-regulate hK2 (KLK2) expression in vivo. hu11B6 demonstrates exquisite targeting specificity for KLK2. A single administration of actinium-225 labeled hu11B6 eradicates disease and significantly prolongs survival in animal models. DNA damage arising from alpha particle irradiation induces AR and subsequently KLK2, generating a unique feed-forward mechanism, which increases binding of hu11B6. Imaging data in nonhuman primates support the possibility of utilizing hu11B6 in man.
Pharmacology, Toxicology and Pharmaceutical Science
2
3%
Other
6
8%
Unknown
31
41%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 15. 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 03 September 2024.
All research outputs
#2,934,216
of 31,439,095 outputs
Outputs from Nature Communications
#36,872
of 76,086 outputs
Outputs of similar age
#47,268
of 354,722 outputs
Outputs of similar age from Nature Communications
#636
of 1,158 outputs
Altmetric has tracked 31,439,095 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 76,086 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 51.3. This one has gotten more attention than average, scoring higher than 51% 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 354,722 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 1,158 others from the same source and published within six weeks on either side of this one. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
