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Monoclonal and Polyclonal Antibodies Research / HER2/EGFR in Cancer Research · Journal article
Clinical Cancer Research · August 18, 2026
Encouraging direction, but not yet definitive.
A preclinical study demonstrating that the actinium-225-labeled anti-MUC-16 radioimmunoconjugate achieves complete remission or durable tumor control in MUC-16-expressing ovarian and pancreatic cancer xenografts, with acceptable safety in naive mice. The result is MUC-16 expression-dependent and warrants clinical translation, but remains a proof-of-concept in animal models.
Preclinical in vivo efficacy and safety study using cell line-derived and patient-derived xenograft models. Mice (immunocompromised, bearing MUC-16-positive human cancer xenografts) and healthy mice for safety studies. Tumors expressed MUC-16 at high, medium, or low levels.. Intervention: [225Ac]Ac-Macropa-M16AB radioimmunoconjugate at 13, 18.6, or 15 kBq doses administered intravenously (doses and schedule inferred), two or three doses 10 days apart. Compared with: Untreated control animals (no further details on control intervention provided).
In SW1990 CDX models, 16.7% of mice achieved complete remission and 83.3% showed durable tumor growth suppression for ≥50 days versus rapid progression in controls 100% sustained complete remissions achieved in high and medium-MUC-16-expressing EOC and PDAC PDXs In low MUC-16-expressing EOC PDX, treatment demonstrated tumor growth inhibition and prolonged survival
Preclinical animal models; direct translation to human efficacy and tolerability unknown Long-term toxicity and organ-specific dose-limiting effects not characterized beyond histopathology
These results suggest potential clinical benefit for EOC and PDAC patients with MUC-16-positive tumors, but clinical translation requires human trials to confirm efficacy, determine optimal dosing, and establish true safety. MUC-16 expression level may be a relevant biomarker for patient selection.
Sound preclinical efficacy in multiple xenograft models with dose-dependent activity and acceptable safety, but limited to in vivo animal studies without human data.
As stated by the source record.
Quoted from the source exactly as published.
These results suggest potential clinical benefit for EOC and PDAC patients with MUC-16-positive tumors, but clinical translation requires human trials to confirm efficacy, determine optimal dosing, and establish true safety. MUC-16 expression level may be a relevant biomarker for patient selection.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Abstract Purpose: MUC-16-targeted antibodies can deliver contrast agents (diagnostic) and/or cytotoxic payloads (therapy) to the tumor site. MUC-16 is overexpressed in 80% of epithelial ovarian cancer (EOC) and 65% of pancreatic ductal adenocarcinomas (PDAC). We previously developed a fully human antibody against MUC-16 (M16AB) and demonstrated the utility of [89Zr]Zr-DFO-M16AB as a PET imaging agent. Here, we developed [225Ac]Ac-Macropa-M16AB radioimmunoconjugate (RIC) and studied its efficacy against MUC-16-positive EOC and PDAC xenografts. Experimental design: [225Ac]Ac-Macropa-M16AB was characterized in vitro. The pharmacokinetics, biodistribution, hematological safety and dosimetry of [225Ac]Ac-Macropa-M16AB were studied in healthy mice. The efficacy of two doses (13 or 18.6 kBq) [225Ac]Ac-Macropa-M16AB administered at 10 days apart was evaluated in MUC-16-expressing cell line-derived xenograft (CDX) SW1990 and mice bearing PDAC and EOC patient-derived xenografts (PDX) with varying MUC-16 expression levels. Results: In SW1990 CDX models [225Ac]Ac-Macropa-M16AB induced complete remission (CR) in 16.7% of mice, while the remaining 83.3% exhibited durable tumor growth suppression for ≥ 50 days, whereas all control animals progressed rapidly. [225Ac]Ac-Macropa-M16AB treatment resulted in 100% sustained CRs in high and medium-MUC16-expressing EOC and PDAC PDXs. While in the low MUC-16 expressing EOC PDX, the treatment demonstrated tumor growth inhibition and prolonged survival. [225Ac]Ac-Macropa-M16AB (3 x 15 kBq) administered in naive mice, 10-d apart was tolerated biochemically and haematologically, with only mild, dose-dependent hepatic and splenic changes observed on histopathology. Conclusion: The effectiveness of[225Ac]Ac-Macropa-M16AB which is dependent on the expression levels of MUC-16 indicates potential benefits for EOC and PDAC patients when translated in clinical trials.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.