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Therapeutic Potential of the 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 one of the oncoplacental genes ectopically expressed in various cancers. Antibody-drug conjugates (ADC) have the potential to substantially improve efficacy and reduce toxicity of treatment compared with cytotoxic small-molecule drugs. They have recently been employed to treat cancers. Objective: To examine the efficacy of an SN38-conjugated monoclonal anti-PLAC1 antibody in breast cancer. Methods: Anti-human PLAC1 monoclonal antibodies were produced and characterized. SN38 was conjugated to an anti-PLAC1 antibody (clone: 2H12C12) and conjugation efficacy was evaluated by UV spectrophotometry. Post-conjugation reactivity was then tested using ELISA and flow cytometry. In vitro, cytotoxicity profiling of 2H12C12-SN38 was examined on MDA-MB-231 breast cancer cells using a fluorimetric assay. The effect of 2H12C12-SN38 on MDA-MB-231 tumor growth and angiogenesis ex vivo was tested by chorioallantoic membrane (CAM) assay followed by immunohistochemical analysis of the tumor. Pharmacokinetics of 2H12C12-SN38 in mice was measured by successive venipuncture after ADC administration. Inhibitory effects of anti-PLAC1 ADC on tumor growth were assessed in a nude mice xenograft model of human breast cancer. Results: Anti-PLAC1 ADC exerted a substantial cytotoxicity on MDA-MB-231 cells starting from a concentration of about 33 nM. ADC also significantly decreased the growth of MDA-MB-231 tumors on CAM assay but did not show a significant effect on tumor angiogenesis. Pharmacokinetics of anti-PLAC1 ADC in mice showed an average half-life (t1/2) of about 80 hours. Conclusion: Treatment of nude mice with ADC resulted in a significant decrease in tumor size compared to isotype-matched antibody-SN38 conjugate, unconjugated anti-PLAC1 antibody, or free SN38. | ||
| کلیدواژهها | ||
| Breast cancer؛ CAM؛ Placenta-specific 1 (PLAC1)؛ SN38؛ Tumorigenesis | ||
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آمار تعداد مشاهده مقاله: 10 |
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