Potency and safety of novel [Ac]Ac-labeled pertuzumab-PEGylated emtansine drug conjugate against HER2-positive breast cancer.
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OpenAlex 토픽 ·
HER2/EGFR in Cancer Research
Radiopharmaceutical Chemistry and Applications
Peptidase Inhibition and Analysis
[PURPOSE] Approved therapeutics targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) have unacceptably high recurrence rates.
APA
Jessica Pougoue Ketchemen, Alissar Monzer, et al. (2026). Potency and safety of novel [Ac]Ac-labeled pertuzumab-PEGylated emtansine drug conjugate against HER2-positive breast cancer.. British journal of cancer. https://doi.org/10.1038/s41416-026-03393-2
MLA
Jessica Pougoue Ketchemen, et al.. "Potency and safety of novel [Ac]Ac-labeled pertuzumab-PEGylated emtansine drug conjugate against HER2-positive breast cancer.." British journal of cancer, 2026.
PMID
41946831 ↗
Abstract 한글 요약
[PURPOSE] Approved therapeutics targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) have unacceptably high recurrence rates. HER2 is amplified and overexpressed in 25-30% of BC. Actinium-225 (Ac) has ideal decay characteristics for targeted alpha therapy. To improve the therapeutic index, we describe the effectiveness and safety of an anti-HER2 antibody-drug radioconjugate (ADR) [Ac]Ac-Macropa-pertuzumab-PEG-DM1.
[AIM] To evaluate the effectiveness and safety of [Ac]Ac-Macropa-pertuzumab-PEG-DM1 against HER2-positive BC.
[EXPERIMENTAL DESIGN] The antibody-drug conjugate (ADC) pertuzumab-PEG-DM1 and the ADR [Ac]Ac-Macropa-pertuzumab-PEG-DM1 were developed. Safety and biodistribution were carried out in healthy female Balb/C mice and in mice bearing HCC1954/JIMT-1 xenografts, respectively. Radioimmunotherapy was done in nude mice bearing trastuzumab-resistant HCC1954 (high HER2-density), T-DM1/trastuzumab-resistant JIMT-1 (medium HER2-density) and MDA-MB-468 (negative control with very low HER2-density) xenografts.
[RESULTS] Internalisation in HCC1954 and JIMT-1 cells was HER2 density-dependent, with pertuzumab-PEG-DM1 2.5-22-fold higher than unconjugated pertuzumab. Pertuzumab-PEG-DM1 (8 mg/kg) and [Ac]Ac-Macropa-pertuzumab-PEG-DM1 (18 kBq) administered separately in healthy Balb/C mice, 10-days apart was well tolerated biochemically and haematologically for 20-days. Mice bearing HCC1954 tumours treated using [Ac]Ac-Macropa-pertuzumab-PEG-DM1 and pertuzumab-PEG-DM1 all had complete remissions, whereas those bearing JIMT-1 tumour showed significant % tumour growth inhibition of 72.1 and 29.4%, respectively.
[CONCLUSION] [Ac]Ac-Macropa-pertuzumab-PEG-DM1 is more potent than pertuzumab-PEG-DM1 against trastuzumab or T-DM1-resistant BC necessitating clinical investigation.
[AIM] To evaluate the effectiveness and safety of [Ac]Ac-Macropa-pertuzumab-PEG-DM1 against HER2-positive BC.
[EXPERIMENTAL DESIGN] The antibody-drug conjugate (ADC) pertuzumab-PEG-DM1 and the ADR [Ac]Ac-Macropa-pertuzumab-PEG-DM1 were developed. Safety and biodistribution were carried out in healthy female Balb/C mice and in mice bearing HCC1954/JIMT-1 xenografts, respectively. Radioimmunotherapy was done in nude mice bearing trastuzumab-resistant HCC1954 (high HER2-density), T-DM1/trastuzumab-resistant JIMT-1 (medium HER2-density) and MDA-MB-468 (negative control with very low HER2-density) xenografts.
[RESULTS] Internalisation in HCC1954 and JIMT-1 cells was HER2 density-dependent, with pertuzumab-PEG-DM1 2.5-22-fold higher than unconjugated pertuzumab. Pertuzumab-PEG-DM1 (8 mg/kg) and [Ac]Ac-Macropa-pertuzumab-PEG-DM1 (18 kBq) administered separately in healthy Balb/C mice, 10-days apart was well tolerated biochemically and haematologically for 20-days. Mice bearing HCC1954 tumours treated using [Ac]Ac-Macropa-pertuzumab-PEG-DM1 and pertuzumab-PEG-DM1 all had complete remissions, whereas those bearing JIMT-1 tumour showed significant % tumour growth inhibition of 72.1 and 29.4%, respectively.
[CONCLUSION] [Ac]Ac-Macropa-pertuzumab-PEG-DM1 is more potent than pertuzumab-PEG-DM1 against trastuzumab or T-DM1-resistant BC necessitating clinical investigation.