Int J Med Sci 2019; 16(9):1188-1198. doi:10.7150/ijms.35452 This issue Cite

Research Paper

Evaluation of a novel monoclonal antibody against tumor-associated MUC1 for diagnosis and prognosis of breast cancer

Natascha Stergiou1✉, Johannes Nagel2, Stefanie Pektor3, Anne-Sophie Heimes4, Jörg Jäkel5, Walburgis Brenner4, Marcus Schmidt4, Matthias Miederer3, Horst Kunz6, Frank Roesch2*, Edgar Schmitt1✉*

1. Institute for Immunology, University Medical Center;
2. Institute for Nuclear chemistry, Johannes-Gutenberg University;
3. Clinic and Polyclinic for Nuclear Medicine, University Medical Center;
4. Department of Obstetrics and Women's Health, University Medical Center, Johannes Gutenberg-University, Germany,
5. Department of Pathology, University Medical Center;
6. Institute for Organic Chemistry, Johannes-Gutenberg University.
*joint senior author

Citation:
Stergiou N, Nagel J, Pektor S, Heimes AS, Jäkel J, Brenner W, Schmidt M, Miederer M, Kunz H, Roesch F, Schmitt E. Evaluation of a novel monoclonal antibody against tumor-associated MUC1 for diagnosis and prognosis of breast cancer. Int J Med Sci 2019; 16(9):1188-1198. doi:10.7150/ijms.35452. https://www.medsci.org/v16p1188.htm
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Abstract

There is still a great unmet medical need concerning diagnosis and treatment of breast cancer which could be addressed by utilizing specific molecular targets. Tumor-associated MUC1 is expressed on over 90 % of all breast cancer entities and differs strongly from its physiological form on epithelial cells, therefore presenting a unique target for breast cancer diagnosis and antibody-mediated immune therapy. Utilizing an anti-tumor vaccine based on a synthetically prepared glycopeptide, we generated a monoclonal antibody (mAb) GGSK-1/30, selectively recognizing human tumor-associated MUC1. This antibody targets exclusively tumor-associated MUC1 in the absence of any binding to MUC1 on healthy epithelial cells thus enabling the generation of breast tumor-specific radiolabeled immune therapeutic tools.

Methods: MAb GGSK-1/30 was used for immunohistochemical analysis of human breast cancer tissue. Its desferrioxamine (Df')-conjugate was synthesized and labelled with 89Zr. [89Zr]Zr-Df'-GGSK-1/30 was evaluated as a potential PET tracer. Binding and pharmacokinetic properties of [89Zr]Zr-Df'-GGSK-1/30 were analyzed in vitro using human and murine cell lines that express tumor-associated MUC1. Self-generated primary murine breast cancer cells expressing human tumor-associated MUC1 were transplanted subcutaneously in wild type and human MUC1-transgenic mice. The pharmacology of [89Zr]Zr-Df'-GGSK-1/30 was investigated using breast tumor-bearing mice in vivo by PET/MRT imaging as well as by ex vivo organ biodistribution analysis.

Results: The mAb GGSK-1/30 stained specifically human breast tumor tissue and can be possibly used to predict the severity of disease progression based on the expression of the tumor-associated MUC1. For in vivo imaging, the Df'-conjugated mAb was radiolabeled with a radiochemical yield of 60 %, a radiochemical purity of 95 % and an apparent specific activity of 6.1 GBq/µmol. After 7 d, stabilities of 84 % in human serum and of 93 % in saline were observed. In vitro cell studies showed strong binding to human tumor-associated MUC1 expressing breast cancer cells. The breast tumor-bearing mice showed an in vivo tumor uptake of >50 %ID/g and clearly visible specific enrichment of the radioconjugate via PET/MRT.

Principal conclusions: Tumor-associated MUC1 is a very important biomarker for breast cancer next to the traditional markers estrogen receptor (ER), progesterone receptor (PR) and HER/2-neu. The mAb GGSK-1/30 can be used for the diagnosis of over 90% of breast cancers, including triple negative breast cancer based on biopsy staining. Its radioimmunoconjugate represents a promising PET-tracer for breast cancer imaging selectively targeting breast cancer cells.

Keywords: MUC1, breast cancer diagnosis, mAb, 89Zr


Citation styles

APA
Stergiou, N., Nagel, J., Pektor, S., Heimes, A.S., Jäkel, J., Brenner, W., Schmidt, M., Miederer, M., Kunz, H., Roesch, F., Schmitt, E. (2019). Evaluation of a novel monoclonal antibody against tumor-associated MUC1 for diagnosis and prognosis of breast cancer. International Journal of Medical Sciences, 16(9), 1188-1198. https://doi.org/10.7150/ijms.35452.

ACS
Stergiou, N.; Nagel, J.; Pektor, S.; Heimes, A.S.; Jäkel, J.; Brenner, W.; Schmidt, M.; Miederer, M.; Kunz, H.; Roesch, F.; Schmitt, E. Evaluation of a novel monoclonal antibody against tumor-associated MUC1 for diagnosis and prognosis of breast cancer. Int. J. Med. Sci. 2019, 16 (9), 1188-1198. DOI: 10.7150/ijms.35452.

NLM
Stergiou N, Nagel J, Pektor S, Heimes AS, Jäkel J, Brenner W, Schmidt M, Miederer M, Kunz H, Roesch F, Schmitt E. Evaluation of a novel monoclonal antibody against tumor-associated MUC1 for diagnosis and prognosis of breast cancer. Int J Med Sci 2019; 16(9):1188-1198. doi:10.7150/ijms.35452. https://www.medsci.org/v16p1188.htm

CSE
Stergiou N, Nagel J, Pektor S, Heimes AS, Jäkel J, Brenner W, Schmidt M, Miederer M, Kunz H, Roesch F, Schmitt E. 2019. Evaluation of a novel monoclonal antibody against tumor-associated MUC1 for diagnosis and prognosis of breast cancer. Int J Med Sci. 16(9):1188-1198.

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