Abstract LB-051: Cancer cell binding, internalization and intracellular localization of a novel therapeutic peptide SOR-C13 targeting the TRPV6 oncochannel
Bibliographic record
Abstract
Abstract SOR-C13, a 13-mer peptide derived from soricidin, the paralytic protein component of saliva of the Northern Short-tailed shrew, has recently completed a phase I clinical trial for the treatment of epithelial-derived cancers. SOR-C13 specifically targets and inhibits the TRPV6 calcium channel - a recognized oncochannel over-expressed in a number of epithelial cancers (e.g. breast, ovarian, prostate). SOR-C13 is the first TRPV6-targeting drug to enter clinical development. Xenograft and fluorescent imaging studies provide in vivo evidence of SOR-C13 efficacy in a range of epithelial tumors as well as SOR-C13's preferential accumulation at tumour sites. To demonstrate the specificity of the peptide for TRPV6 and determine its fate, modified SOR-C13 peptide was labeled with fluorescein to enable monitoring of cellular binding and internalization in high versus low TRPV6 cancer cell lines. Various organelle-specific fluorescent trackers for nuclei, actins, lysosomes, and endoplasmic reticula were paired with labeled SOR-C13 peptides and anti-TRPV6 antibody in fluorescence imaging studies to monitor intracellular trafficking. Rapid peptide binding and internalization was observed on incubation of fluorescently labeled SOR-C13 with a breast cancer cell line (T-47D) expressing high levels of the ion channel. Significantly less SOR-C13 binding was observed in an ovarian cancer cell line (SKOV-3) with low TRPV6 levels. Fluorescently labeled SOR-C13 scramble peptide was included as a control and did not bind to high TRPV6 cells. Co-localization studies did not demonstrate a clear association of the fluorescently labeled SOR-C13 with lysosomes, the ER or actin. This study demonstrates that SOR-C13 not only specifically binds to TRPV6-expressing cancer cells according to their level of TRPV6 expression but is also internalized. The correlation of TRPV6 expression in tumors and clinical efficacy will be evaluated during the next SOR-C13 clinical trials. Additionally, these results set the stage for further development of SOR-C13-based peptide drug conjugates for TRPV6 targeted anti-cancer therapies. Citation Format: Michelle Davey, Dominique Dugourd, Tyler Lutes, Christopher Rice, Sean Gormley, Stephanie St. Pierre, John M. Stewart. Cancer cell binding, internalization and intracellular localization of a novel therapeutic peptide SOR-C13 targeting the TRPV6 oncochannel. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-051.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".