Modeling antibody drug conjugate potential using a granzyme B antibody fusion protein.
Antibody drug conjugate
Antibody fusion protein
Granzyme B
Journal
BMC biology
ISSN: 1741-7007
Titre abrégé: BMC Biol
Pays: England
ID NLM: 101190720
Informations de publication
Date de publication:
14 Mar 2024
14 Mar 2024
Historique:
received:
11
09
2023
accepted:
05
03
2024
medline:
18
3
2024
pubmed:
15
3
2024
entrez:
15
3
2024
Statut:
epublish
Résumé
Antibody drug conjugates (ADCs) constitute a promising class of targeted anti-tumor therapeutics that harness the selectivity of monoclonal antibodies with the potency of cytotoxic drugs. ADC development is best suited to initially screening antibody candidates for desired properties that potentiate target cell cytotoxicity. However, validating and producing an optimally designed ADC requires expertise and resources not readily available to certain laboratories. In this study, we propose a novel approach to help streamline the identification of potential ADC candidates by utilizing a granzyme B (GrB)-based antibody fusion protein (AFP) for preliminary screening. GrB is a non-immunogenic serine protease expressed by immune effector cells such as CD8 + T cells that induces apoptotic activity and can be leveraged for targeted cell killing. Our innovative model allows critical antibody parameters (including target cell binding, internalization, and cytotoxic potential) to be more reliably evaluated in vitro through the creation of an ADC surrogate. Successful incorporation of this AFP could also significantly expand and enhance ADC development pre-clinically, ultimately leading to the accelerated translation of ADC therapies for patients.
Sections du résumé
BACKGROUND
BACKGROUND
Antibody drug conjugates (ADCs) constitute a promising class of targeted anti-tumor therapeutics that harness the selectivity of monoclonal antibodies with the potency of cytotoxic drugs. ADC development is best suited to initially screening antibody candidates for desired properties that potentiate target cell cytotoxicity. However, validating and producing an optimally designed ADC requires expertise and resources not readily available to certain laboratories.
RESULTS
RESULTS
In this study, we propose a novel approach to help streamline the identification of potential ADC candidates by utilizing a granzyme B (GrB)-based antibody fusion protein (AFP) for preliminary screening. GrB is a non-immunogenic serine protease expressed by immune effector cells such as CD8 + T cells that induces apoptotic activity and can be leveraged for targeted cell killing.
CONCLUSIONS
CONCLUSIONS
Our innovative model allows critical antibody parameters (including target cell binding, internalization, and cytotoxic potential) to be more reliably evaluated in vitro through the creation of an ADC surrogate. Successful incorporation of this AFP could also significantly expand and enhance ADC development pre-clinically, ultimately leading to the accelerated translation of ADC therapies for patients.
Identifiants
pubmed: 38486229
doi: 10.1186/s12915-024-01860-x
pii: 10.1186/s12915-024-01860-x
pmc: PMC10941411
doi:
Substances chimiques
Immunoconjugates
0
Granzymes
EC 3.4.21.-
alpha-Fetoproteins
0
Antineoplastic Agents
0
Antibodies, Monoclonal
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
66Subventions
Organisme : NCI NIH HHS
ID : R15 CA215874
Pays : United States
Organisme : NIH HHS
ID : R15 CA215874
Pays : United States
Informations de copyright
© 2024. The Author(s).
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