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A Rational Designed Novel Bispecific Antibody for the Treatment of GBM
- Source :
- Biomedicines, Volume 9, Issue 6, Biomedicines, Vol 9, Iss 640, p 640 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI, 2021.
-
Abstract
- Epidermal growth factor receptor variant III (EGFRvIII) is highly and specifically expressed in a subset of lethal glioblastoma (GBM), making the receptor a unique therapeutic target for GBM. Recently, bispecific antibodies (BsAbs) have shown exciting clinical benefits in cancer immunotherapy. Here, we report remarkable results for GBM treatment with a BsAb constructed by the “BAPTS” method. The BsAb was characterized through LC/MS, SEC-HPLC, and SPR. Furthermore, the BsAb was evaluated in vitro for bioactivities through FACS, antigen-dependent T-cell-mediated cytotoxicity, and a cytokine secretion assay, as well as in vivo for antitumor activity and pharmacokinetic (PK) parameters through immunodeficient NOD/SCID and BALB/c mouse models. The results indicated that the EGFRvIII-BsAb eliminated EGFRvIII-positive GBM cells by recruiting and stimulating effector T cells secreting cytotoxic cytokines that killed GBM cells in vitro. The results demonstrated the antitumor potential and long circulation time of EGFRvIII-BsAb in NOD/SCID mice bearing de2–7 subcutaneously heterotopic transplantation tumors and BALB/c mice. In conclusion, our experiments in both in vitro and in vivo have shown the remarkable antitumor activities of EGFRvIII-BsAb, highlighting its potential in clinical applications for the treatment of GBM. Additional merits, including a long circulation time and low immunogenicity, have also made the novel BsAb a promising therapeutic candidate.
- Subjects :
- EGFRvIII
biology
business.industry
QH301-705.5
medicine.medical_treatment
Immunogenicity
Medicine (miscellaneous)
Nod
GBM
General Biochemistry, Genetics and Molecular Biology
In vitro
Article
bispecific antibody
Cancer immunotherapy
In vivo
split intein
Cancer research
biology.protein
Cytotoxic T cell
Medicine
Cytokine secretion
Epidermal growth factor receptor
Biology (General)
business
Subjects
Details
- Language :
- English
- ISSN :
- 22279059
- Volume :
- 9
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Biomedicines
- Accession number :
- edsair.doi.dedup.....2d70996a0b5e285e92d1c4d0b63551be