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Fusion of apoptosis‐related protein Cytochrome c with anti‐HER‐2 single‐chain antibody targets the suppression of HER‐2+ breast cancer
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15824934 and 15821838
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....18508b6aee552aacab818290e61766bc
- Full Text :
- https://doi.org/10.1111/jcmm.17001