scholarly journals A novel humanized MUC1 antibody–drug conjugate for the treatment of trastuzumab-resistant breast cancer

2021 ◽  
Author(s):  
Guang Wu ◽  
Lan Li ◽  
Yuxin Qiu ◽  
Wei Sun ◽  
Tianhao Ren ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibody ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Xenograft Model ◽  
Therapeutic Drug ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Her2 Breast Cancer ◽  
Antibody Drug

Abstract Mucin 1 (MUC1) has been regarded as an ideal target for cancer treatment, since it is overexpressed in a variety of different cancers including the majority of breast cancer. However, there are still no approved monoclonal antibody drugs targeting MUC1. In this study, we generated a humanized MUC1 (HzMUC1) antibody from our previously developed MUC1 mouse monoclonal antibody that only recognizes MUC1 on the surface of tumor cells. Furthermore, an antibody–drug conjugate (ADC) was generated by conjugating HzMUC1 with monomethyl auristatin (MMAE), and the efficacy of HzMUC1-MMAE on the MUC1-positive HER2+ breast cancer in vitro and in ‘Xenograft’ model was tested. Results from western blot analysis and immunoprecipitation revealed that the HzMUC1 antibody did not recognize cell-free MUC1-N in sera from breast cancer patients. Confocal microscopy analysis showed that HzMUC1 antibody bound to MUC1 on the surface of breast cancer cells. Results from mapping experiments suggested that HzMUC1 may recognize an epitope present in the interaction region between MUC1-N and MUC1-C. Results from colony formation assay and flow cytometry demonstrated that HzMUC1-MMAE significantly inhibited cell growth by inducing G2/M cell cycle arrest and apoptosis in trastuzumab-resistant HER2-positive breast cancer cells. Meanwhile, HzMUC1-MMAE significantly reduced the growth of HCC1954 xenograft tumors by inhibiting cell proliferation and enhancing cell death. In conclusion, our results indicate that HzMUC1-ADC is a novel therapeutic drug that can overcome trastuzumab resistance of breast cancer. HzMUC1-ADC should also be an effective therapeutic drug for the treatment of different MUC1-positive cancers in clinic.

Abstract 741: Targeting trastuzumab and T-DM-1 resistant breast cancer cells with EV20/MMAF, an antibody drug-conjugate against HER3

2018 ◽  
Author(s):  
Gianluca Sala ◽  
Lucia Gandullo ◽  
Emily Capone ◽  
Maria Elena Diaz-Rodriguez ◽  
Daniela D'Agostino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Antibody Drug

scholarly journals Antibody-drug conjugate T-DM1 treatment for HER2+ breast cancer induces ROR1 and confers resistance through activation of Hippo transcriptional coactivator YAP1

EBioMedicine ◽  
2019 ◽  
Vol 43 ◽  
pp. 211-224 ◽  
Author(s):  
Syed S. Islam ◽  
Mohammed Uddin ◽  
Abu Shadat M. Noman ◽  
Hosneara Akter ◽  
Nusrat J. Dity ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcriptional Coactivator ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Her2 Breast Cancer ◽  
Antibody Drug

Bstronximab, a novel therapeutic antibody to treat metastatic testis cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15621-e15621
Author(s):  
William Michael Schopperle
Keyword(s):  
Monoclonal Antibody ◽  
Metastatic Cancer ◽  
Therapeutic Antibody ◽  
Therapeutic Drug ◽  
Testis Cancer ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Current Therapies ◽  
Antibody Drug ◽  
Novel Therapeutic

e15621 Background: The treatment of metastatic testis cancer is by far the gold standard for treating metastatic solid cancers: over 90% of men diagnosis with metastatic testis cancer are completely cured with current therapies. What seems to be lost and somewhat surprising within this truly remarkable therapeutic cancer success in treating a metastatic cancer is the fact that in United States alone there are still over 400 young men who died from this disease because they do not respond to current therapies. Thus, despite the tremendous clinical success with treating this disease, there is still a strong unmet need to develop new treatments for men with metastatic testis cancer who fall outside the celebration of this disease as being completely cured. Methods: The human germ cell tumor embryonal carcinoma line, TERA-1. was used to generate purified testis cancer-specific cell membrane antigens to immunize mice and generated antibodies, by standard conventional mouse B cell hybridoma protocols. Isolated monoclonal antibodies where tested by ELISA and SDS-PAGE Western blotting to identify testis cancer specific antibodies. Testis cancer positive antibodies were further screen in an antibody-drug-conjugate screen to determine if the monoclonal antibody could function as a antibody-drug-conjugate therapeutic drug for metastatic testis cancer. Results: Dozens of monoclonal antibodies were generated with our antibody screen. Based on the screen results, a lead monoclonal antibody, named Bstrongomab, was selected for further development as a testis cancer therapeutic antibody. Bstrongomab is an IgG1 monoclonal antibody specific to the human embryonic cell marker, and testis cancer marker, TRA-1-60, a carbohydrate molecule which has been identified over 4 decades ago as a true human testis cancer marker. A human/mouse chimeric version of Bstrongomab was created - Bstrongximab - as a human therapeutic antibody. An antibody-drug-conjugate using Bstrongximab and the toxic payload MMAE (Monomethyl auristatin E) was developed and tested in pre-clinical human cancer testis in-vitro and in-vivo models and showed to be a powerful testis cancer therapeutic drug targeting TRA-1-60. Conclusions: Bstrongximab-MMAE is a novel therapeutic antibody-drug-conjugate which targets the testis cancer antigen TRA-1-60. TRA-1-60 is not expressed in normal tissues. Bstrongximab-MMAE is a new cancer drug ready to move into clinical trials for men with metastatic cancer that do not respond with current therapy protocols.

Marriage of antibody–drug conjugate with gold nanorods to achieve multi-modal ablation of breast cancer cells and enhanced photoacoustic performance

RSC Advances ◽  
2016 ◽  
Vol 6 (52) ◽  
pp. 46594-46606 ◽  
Author(s):  
Fei Cao ◽  
Qian Yao ◽  
Tieshan Yang ◽  
Zhao Zhang ◽  
Yu Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Therapy ◽  
Gold Nanorods ◽  
Photothermal Therapy ◽  
Breast Cancer Cells ◽  
Antibody Therapy ◽  
Active Targeting ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Antibody Drug

A multifunctional nano platform against cancer using SiO2-coated gold nanorods and antibody–drug conjugate is constructed. It incorporates active targeting, antibody therapy, drug therapy, photothermal therapy, and enhanced photoacoustic performance.

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