Fusion of apoptosis‐related protein Cytochrome c with anti‐HER‐2 single‐chain antibody targets the suppression of HER‐2+ breast cancer
Autor: | Yunfeng Hu, Zihui Zheng, Min Wang, Chen Jiahui, Yichen Guo, Jun Guo, Chen Li, Dandan Lu, Abhishek Gangrade |
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Rok vydání: | 2021 |
Předmět: |
Cell Survival
Receptor ErbB-2 Recombinant Fusion Proteins medicine.medical_treatment immunoapoptotic molecules Apoptosis scFv Targeted therapy Mice breast cancer Antineoplastic Agents Immunological Breast cancer Immune system Antibody Specificity Immunotoxin Cell Line Tumor Gene Order medicine Animals Humans Fragmentation (cell biology) Cell Proliferation biology Chemistry Cytochrome c HER‐2 Cytochromes c Original Articles Cell Biology targeted therapy Flow Cytometry medicine.disease Xenograft Model Antitumor Assays Disease Models Animal biology.protein Cancer research Molecular Medicine Original Article Female Antibody Apoptosis Regulatory Proteins Plasmids Single-Chain Antibodies |
Zdroj: | Journal of Cellular and Molecular Medicine |
ISSN: | 1582-4934 1582-1838 |
Popis: | Cancer treatment has gradually developed from toxic chemotherapy to targeted therapy with fewer side effects. Approximately 30% of breast cancer patients overexpress human epidermal growth factor receptor 2 (HER‐2). Previous studies have successfully produced single‐chain antibodies (scFv) targeting HER‐2+ breast cancer; however, scFv have poor stability, easy aggregation and a shorter half‐life, which have no significant effect on targeting therapy. Moreover, scFv has been considered as a drug delivery platform that can kill target cells by effector molecules. However, the functional killing domains of immunotoxins are mainly derived from plant or bacterial toxins, which have a large molecular weight, low tissue permeability and severe side effects. To address these concerns, we designed several apoptotic immune molecules to replace exogenous toxins using endogenous apoptosis‐related protein DNA fragmentation factor 40 (DFF40) and tandem‐repeat Cytochrome c base on caspase‐3 responsive peptide (DEVD). Our results suggest that DFF40 or Cytc fusion scFv specifically targets HER‐2 overexpressing breast cancer cells (SK‐BR‐3 and BT‐474) rather than HER‐2 negative cells (MDA‐MB‐231 and MCF‐7). Following cellular internalization, apoptosis‐related proteins inhibited tumour activity by initiating endogenous apoptosis pathways, which significantly reduced immunogenicity and toxic side effects. Therefore, we suggest that immunoapoptotic molecules may become potential drugs for targeted immunotherapy of breast cancer. |
Databáze: | OpenAIRE |
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