Prospective effect of linkers type on the anticancer activity of pemetrexed-monoclonal antibody (atezolizumab) conjugates.
antibody drug conjugate
monoclonal antibody
pemetrexed
Journal
F1000Research
ISSN: 2046-1402
Titre abrégé: F1000Res
Pays: England
ID NLM: 101594320
Informations de publication
Date de publication:
2023
2023
Historique:
accepted:
07
03
2024
medline:
14
8
2024
pubmed:
14
8
2024
entrez:
14
8
2024
Statut:
epublish
Résumé
Conventional chemotherapy results in severe toxic side effects due to affecting normal and cancer cells. The conjugation of chemotherapy with mAb will improve the chemotherapy selectivity towards cancer cells and at the same time will potentiate immune system to detect and kill cancer cells. The aim of the study was to prepare atezolizumab-pemetrexed conjugate using two types of linkers (linker conjugated with -NH2 of lysine amino acid in the mAb). This study utilizes (for the first time) the mAb atezolizumab (AtZ) to prepare a new, selective conjugate carrier for pemetrexed (PMX) by using gamma amino butyric acid (GABA) as linker for the first time in comparison to the commonly used linker polyethylene glycol (PEG) using carbodiimide (EDC) / N-hydroxysulfosuccinimide (Sulfo-NHS) zero length cross linker. Stepwise evaluation for PMX-linkers linkage as well as mAb conjugates was evaluated by FTIR, The work revealed that two molecules of GABA combined with PMX, which in turn conjugated with an average ratio of 4:1 with mAb, while one molecule of PEG combined with PMX, which in turn conjugated with mAb in the same average ratio. The IC The potential use of such conjugate that selectively directed to the overexpressed lung cells antigen in a low dose leading to reduction of serious side effects of PMX and the cost of therapeutically AtZ mAb used.
Sections du résumé
Background
UNASSIGNED
Conventional chemotherapy results in severe toxic side effects due to affecting normal and cancer cells. The conjugation of chemotherapy with mAb will improve the chemotherapy selectivity towards cancer cells and at the same time will potentiate immune system to detect and kill cancer cells. The aim of the study was to prepare atezolizumab-pemetrexed conjugate using two types of linkers (linker conjugated with -NH2 of lysine amino acid in the mAb).
Methods
UNASSIGNED
This study utilizes (for the first time) the mAb atezolizumab (AtZ) to prepare a new, selective conjugate carrier for pemetrexed (PMX) by using gamma amino butyric acid (GABA) as linker for the first time in comparison to the commonly used linker polyethylene glycol (PEG) using carbodiimide (EDC) / N-hydroxysulfosuccinimide (Sulfo-NHS) zero length cross linker. Stepwise evaluation for PMX-linkers linkage as well as mAb conjugates was evaluated by FTIR,
Results
UNASSIGNED
The work revealed that two molecules of GABA combined with PMX, which in turn conjugated with an average ratio of 4:1 with mAb, while one molecule of PEG combined with PMX, which in turn conjugated with mAb in the same average ratio. The IC
Conclusions
UNASSIGNED
The potential use of such conjugate that selectively directed to the overexpressed lung cells antigen in a low dose leading to reduction of serious side effects of PMX and the cost of therapeutically AtZ mAb used.
Identifiants
pubmed: 39140089
doi: 10.12688/f1000research.140284.2
pmc: PMC11320184
doi:
Substances chimiques
Pemetrexed
04Q9AIZ7NO
Antibodies, Monoclonal, Humanized
0
atezolizumab
52CMI0WC3Y
Antineoplastic Agents
0
Immunoconjugates
0
Antibodies, Monoclonal
0
Polyethylene Glycols
3WJQ0SDW1A
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1197Informations de copyright
Copyright: © 2024 Ibraheem FQ et al.
Déclaration de conflit d'intérêts
No competing interests were disclosed.