Characterization of nanobodies and cannabinoids targeted tyrosine kinase domains of EGFR families for cancer therapy

Name: Thomanai Lamtha

LCSH: Kasetsart University -- Dissertations. Ph.D. (Biochemistry) 2022

Classification :.LCCS: QP606.P78

LCSH: Kasetsart University. -- Department of Biochemistry -- Dissertations

LCSH: Protein-tyrosine kinase

LCSH: Epidermal growth factor

LCSH: Cannabinoids

LCSH: Cancer cells

Abstract: EGFR and HER2 are members of the ErbB tyrosine kinase family, which present some of the most altered proteins in cancer. An aberrant tyrosine kinase activation through gene alterations can drive tumorigenesis and tumor growth. There are many drawbacks with the current anti-HER2 and EGFR drugs, including drug resistance and adverse effects. This study produced the recombinant nanobodies against the HER2-tyrosine kinase (HER2-TK) using phage display technology. The specific anti-HER2-TK nanobody, VHH17, was selected for further characterization. The IC50 of VHH17 exhibited significantly greater HER2 kinase-inhibition activity than the other clones. Consistent with these results, several charges and polar residues of the HER2- TK activation loop that were predicted based on mimotope analysis also appeared in the docking result and interacted via the CDR1, CDR2, and CDR3 loops of VHH17. Furthermore, the cell-penetrable VHH17 (R9VHH17) showed cell-penetrability and significantly decreased HER2-positive cancer cells viability. In addition, the cannabinoids also were studied on the antitumor activity against EGFR-positive cancers. The binding affinities and inhibitory properties of CBD, CBG, and CBN on EGFR-TK were demonstrated. Moreover, these compounds inhibit EGFR-positive epidermoid carcinoma and lung cancer cell growth, which can lead to apoptotic death. This study suggests that the R9VHH17 could be developed as an effective therapeutic agent to treat HER2-positive breast cancers, the CBD and CBG could be developed for EGFR-TKI-based treatment options in patients with EGFR-positive cancers.

Kasetsart University. Office of the University Library

Address: Bangkok

Email: tdckulib@ku.ac.th

Name: Kiattawee Choowongkomon.

Role: Thesis Advisor

Created: 2022

Modified: 2025-07-14

Issued: 2025-07-14

วิทยานิพนธ์/Thesis

application/pdf

URL: https://www.lib.ku.ac.th/KUthesis/2565/thomanai-lam-all.pdf

CallNumber: QP606.P78 .T46

eng

DegreeName: Doctor of Philosophy

Level: Doctoral Degraee

Descipline: Biochemistry

Grantor: Kasetsart University

©copyrights Kasetsart University

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