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- Testing in multiple mouse cancer models demonstrated the platform’s effectiveness across different tumor types.
- To assess the binding affinity of DUNP19, cells were blocked (10% normal goat serum in PBS, 15 min at RT) and incubated with serial dilutions of fluorophore-conjugated DUNP19 or hIgG1 mAb (0.051–1000 ng/mL) in triplicate for 1 h at RT.
- This direct expression pattern may make these types of cancers particularly amenable to LRRC15-targeted therapies, as the therapeutic agent can directly engage with and potentially eliminate the malignant cells.
- For cell classification and identification, Syllogist22 was used to identify signatures present from 43 cell types within normalized gene expression matrices.
- At day 163 post-first injection, mice received an additional 20 MBq 177LuLu-DUNP19 and were re-scanned to detect residual viable HuO9 tumor tissue.
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- Library preparation and sequencing was done with the help of UCLA’s Technology Center for Genomics and Bioinformatics (TCGB).Raw read count RNA-sequencing data were generated from untreated and 177LuLu-DUNP19 treated HuO9 tumors.
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Finally, to capture earlier treatment https://disqus.com/by/aviamastersca/about/ effects, bulk RNA-seq data from U118MG tumors treated with a single injection of RIT and harvest at nadir (30 days p.i.) were collected. Overall, and in line with LRRC15 protein levels (Fig. 1b, c; Supplementary Fig. 6), LRRC15 expression was higher in HuO9 than in U118MG cancer cells, and not quantifiable in HCC1954 cancer cells. D Box-and-whisker plots representing relative transcript expression of LRRC15 (top) and TGFB1 (bottom), comparing untreated tumors to tumors after 177LuLu-DUNP19 therapy. In human cancer cells, RNA-sequencing analysis identified 19,578 protein-coding genes, of which 1985 (HuO9), 1043 (U118MG), and 23 (HCC1954) were differentially expressed genes (DEGs) after 177LuLu-DUNP19 therapy.
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As a beta-particle emitter, Lutetium-177 has the potential to cause DNA strand breaks across a span of 10–50 cell diameters. The longer half-life of full-sized mAbs—conferred by FcRn-mediated recycling—facilitates high tumor retention, which is crucial for therapeutic radionuclides with multi-day half-lives, such as Lutetium-177. These include high binding affinity and exceptional in vivo stability, both of which are essential for sustained target engagement and effective tumor accumulation of radiolabeled compounds. The potential of this technology extends to personalized treatment strategies and dose planning, maximizing the therapeutic index for individual patients.
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