Development of a single-chain fragment variable fused-mutant HALT-1 recombinant immunotoxin against G12V mutated KRAS c olorectal cancer cells.
Autor: | Teo MYM; Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Cheras, Wilayah Persekutuan Kuala Lumpur, Malaysia., Ng JJC; Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Cheras, Wilayah Persekutuan Kuala Lumpur, Malaysia., Fong JY; Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Cheras, Wilayah Persekutuan Kuala Lumpur, Malaysia., Hwang JS; Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, Selangor Darul Ehsan, Malaysia., Song AA; Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang, Selangor, Malaysia., Lim RLH; Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Cheras, Wilayah Persekutuan Kuala Lumpur, Malaysia., In LLA; Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Cheras, Wilayah Persekutuan Kuala Lumpur, Malaysia. |
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Jazyk: | angličtina |
Zdroj: | PeerJ [PeerJ] 2021 Apr 15; Vol. 9, pp. e11063. Date of Electronic Publication: 2021 Apr 15 (Print Publication: 2021). |
DOI: | 10.7717/peerj.11063 |
Abstrakt: | Background: KRAS oncogenes harboring codon G12 and G13 substitutions are considered gatekeeper mutations which drive oncogenesis in many cancers. To date, there are still no target-specific vaccines or drugs available against this genotype, thus reinforcing the need towards the development of targeted therapies such as immunotoxins. Methods: This study aims to develop a recombinant anti-m KRAS scFv-fused mutant Hydra actinoporin-like-toxin-1 (mHALT-1) immunotoxin that is capable of recognizing and eradicating codon-12 mutated k-ras antigen abnormal cells. One G13D peptide mimotope (164-D) and one G12V peptide mimotope (68-V) were designed to elicit antigen specific IgG titres against mutated K-ras antigens in immunised Balb/c mice. The RNA was extracted from splenocytes following ELISA confirmation on post-immunized mice sera and was reverse transcribed into cDNA. The scFv combinatorial library was constructed from cDNA repertoire of variable regions of heavy chain (V Results: The V Discussion: These results suggested that the development of such immunotoxins is potentially useful as an immunotherapeutic application against KRAS -positive malignancies. Competing Interests: The authors declare that they have no competing interests. (© 2021 Teo et al.) |
Databáze: | MEDLINE |
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