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Therapeutic Potential of an Anti-PLAC1 Antibody–Drug Conjugate in a Mouse Model of Human Breast Cancer | ||
| Iranian Journal of Immunology | ||
| دوره 22، شماره 3، آذر 2025، صفحه 2-2 | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22034/iji.2025.106670.3019 | ||
| نویسندگان | ||
| Jafar Mahmoudian1، 2؛ Roya Ghods3، 4؛ Mahmood Jeddi-Tehrani2؛ Nassim Ghaffari-Tabrizi-Wizsy5؛ Mohammad Reza Nejadmoghaddam6؛ Ramin Ghahremanzadeh6؛ Seyed Nasser Ostad1، 7؛ Amir-Hassan Zarnani* 8، 9 | ||
| 1Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences (TUMS), Tehran, Iran. | ||
| 2Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran. | ||
| 3Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran. | ||
| 4Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. | ||
| 5SFL Chicken CAM Lab, Institute of Pathophysiology and Immunology, Medical University of Graz, Graz, 8010, Austria. | ||
| 6Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran. | ||
| 7Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. | ||
| 8Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. | ||
| 9Reproductive Immunology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran. | ||
| چکیده | ||
| Background: Placenta-specific 1 (PLAC1) is an oncoplacental genes aberrantly expressed in various malignancies. Antibody-drug conjugates (ADC) offer a promising therapeutic approach by enhancing efficacy and reducing toxicity of treatment compared to cytotoxic small-molecule agents. Objective: To evaluate the efficacy of an SN38-conjugated monoclonal anti-PLAC1 antibody in a mouse model of breast cancer. Methods: Anti-human PLAC1 monoclonal antibodies were generated and characterized. SN38 was conjugated to an anti-PLAC1 antibody (clone: 2H12C12) and conjugation efficacy was determined by UV spectrophotometry. The antigen-binding activity of the conjugated antibody was assessed using ELISA and flow cytometry. In vitro, the cytotoxic profile of 2H12C12-SN38 was evaluated in MDA-MB-231 breast cancer cells using a fluoroimetric viability assay. The impact of 2H12C12-SN38 on MDA-MB-231 tumor growth and angiogenesis ex vivo was examined using chorioallantoic membrane (CAM) assay followed by immunohistochemical analysis. Pharmacokinetics of 2H12C12-SN38 in mice was determined by serial venipuncture following ADC administration. The inhibitory effects of anti-PLAC1 ADC on tumor growth were evaluated in a nude mouse xenograft model of human breast cancer. Results: The anti-PLAC1 ADC exhibited a substantial cytotoxicity against MDA-MB-231 cells, with effects observed at concentration as low as ~33 nM. In the CAM assay, the ADC significantly reduced the growth of MDA-MB-231 tumor but did not produce a significant effect on tumor angiogenesis. Pharmacokinetic analysis in mice demonstrated an average half-life (t1/2) of approximately 80 hours. In a nude mouse xenograft model, treatment with the ADC resulted in a significant reduction in tumor size compared with isotype-matched antibody-SN38 conjugate, or free SN38. Conclusion: This study represents the first therapeutic application of anti-PLAC1 ADC in a xenograft model of human breast cancer. Our findings support the embryonic origin of cancers and highlight the potential therapeutic value of targeting oncofetal antigens in human breast cancer. | ||
| کلیدواژهها | ||
| Breast cancer؛ CAM؛ Placenta-specific 1 (PLAC1)؛ SN38؛ Tumorigenesis | ||
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آمار تعداد مشاهده مقاله: 255 |
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