AR47A6.4.2, a functional naked monoclonal antibody targeting Trop-2, demonstrates in vivo efficacy in human pancreatic, colon, breast and prostate cancer models
Bibliographic record
Abstract
PR-12 Introduction: Trop-2 is a cell-surface glycoprotein with a putative role in intracellular signal transduction. As a PKC substrate, its cytoplasmic domain has been shown to become phosphorylated, and Trop-2 has been found to induce intracellular calcium signaling. Trop-2 expression has been reported in a large number of human carcinomas, with higher expression being correlated with poor prognosis in colorectal cancer. Using ARIUS’ FunctionFIRST™ platform, AR47A6.4.2, a functional monoclonal antibody targeting Trop-2, was generated. This antibody demonstrated in vitro cytotoxicity in human cancer cell lines and subsequent in vivo efficacy studies conducted to evaluate its therapeutic potential have revealed its anti-tumor activity in human pancreatic cancer models. To extend the utility of AR47A6.4.2 as a therapeutic antibody, in vivo efficacy studies have been expanded to include additional cancer indications, and antibody characterization and mechanism of action studies have been conducted. Method: To investigate the potential anti-tumor effect of this antibody in vivo, AR47A6.4.2 was administered in prophylactic and established xenograft models of human pancreatic, breast, colon and prostate cancer. Immunohistochemical analyses were performed using AR47A6.4.2 to select a relevant pre-clinical toxicology model. To elucidate the mechanism of action of the antibody, a complement-dependent cytotoxicity (CDC) assay on human pancreatic cancer cell lines was conducted. Using a protein profiler array, key signaling molecules were screened in response to AR47A6.4.2 treatment to investigate signal transduction pathways downstream of Trop-2. The affinity of AR47A6.4.2 was also determined by Biacore. Results: AR47A6.4.2 treatment in xenograft models of pancreatic cancer has revealed a significant anti-tumor effect and increased time-to-endpoint. Subsequent efficacy studies in different cancer indications demonstrated significant tumor growth inhibition in human models of breast (90%, p
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".