Antibody-dye Conjugates Targeting EGFR and HER2 for the Photoimmunotherapy of Bladder Cancer.
Bladder cancer
HER2 antigen
cetuximab
epidermal growth factor receptor
photoimmunotherapy
trastuzumab
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
May 2024
May 2024
Historique:
received:
14
03
2024
revised:
27
03
2024
accepted:
28
03
2024
medline:
28
4
2024
pubmed:
28
4
2024
entrez:
27
4
2024
Statut:
ppublish
Résumé
Although there are curative treatment options for non-muscle-invasive bladder cancer, the recurrence of this tumor is high. Therefore, novel targeted therapies are needed for the complete removal of bladder cancer cells in stages of localized disease, in order to avoid local recurrence, to spare bladder cancer patients from stressful and expensive treatment procedures and to increase their quality of life and life expectancy. This study tested a new approach for the photoimmunotherapy (PIT) of bladder cancer. We generated a cysteine modified recombinant version of the antibody cetuximab targeting the epidermal growth factor receptor (EGFR) on the surface of bladder cancer cells. Then, we coupled the novel photoactivatable phthalocyanine dye WB692-CB1 via a maleimide linker to the free cysteines of the antibody. PIT was performed by incubating bladder cancer cells with the antibody dye conjugate followed by irradiation with visible red light. The conjugate was able to induce specific cytotoxicity in EGFR-positive bladder cancer cells in a light dose-dependent manner. Enhanced cytotoxicity in RT112 bladder cancer cells was evoked by addition of a second antibody dye conjugate targeting HER2 or by repeated cycles of PIT. Our new antibody dye conjugate targeting EGFR-expressing bladder cancer cells is a promising candidate for the future PIT of bladder cancer patients.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Although there are curative treatment options for non-muscle-invasive bladder cancer, the recurrence of this tumor is high. Therefore, novel targeted therapies are needed for the complete removal of bladder cancer cells in stages of localized disease, in order to avoid local recurrence, to spare bladder cancer patients from stressful and expensive treatment procedures and to increase their quality of life and life expectancy. This study tested a new approach for the photoimmunotherapy (PIT) of bladder cancer.
MATERIALS AND METHODS
METHODS
We generated a cysteine modified recombinant version of the antibody cetuximab targeting the epidermal growth factor receptor (EGFR) on the surface of bladder cancer cells. Then, we coupled the novel photoactivatable phthalocyanine dye WB692-CB1 via a maleimide linker to the free cysteines of the antibody. PIT was performed by incubating bladder cancer cells with the antibody dye conjugate followed by irradiation with visible red light.
RESULTS
RESULTS
The conjugate was able to induce specific cytotoxicity in EGFR-positive bladder cancer cells in a light dose-dependent manner. Enhanced cytotoxicity in RT112 bladder cancer cells was evoked by addition of a second antibody dye conjugate targeting HER2 or by repeated cycles of PIT.
CONCLUSION
CONCLUSIONS
Our new antibody dye conjugate targeting EGFR-expressing bladder cancer cells is a promising candidate for the future PIT of bladder cancer patients.
Identifiants
pubmed: 38677753
pii: 44/5/1837
doi: 10.21873/anticanres.16985
doi:
Substances chimiques
ErbB Receptors
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
EGFR protein, human
EC 2.7.10.1
Immunoconjugates
0
ERBB2 protein, human
EC 2.7.10.1
Cetuximab
PQX0D8J21J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1837-1844Informations de copyright
Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.