Rapid, site-specific labeling of "off-the-shelf" and native serum autoantibodies with T cell-redirecting domains.
Sci Adv
; 8(18): eabn4613, 2022 May 06.
Article
en En
| MEDLINE
| ID: mdl-35522741
ABSTRACT
Extensive antibody engineering and cloning is typically required to generate new bispecific antibodies. Made-to-order genes, advanced expression systems, and high-efficiency cloning can simplify and accelerate this process, but it still can take months before a functional product is realized. We developed a simple method to site-specifically and covalently attach a T cell-redirecting domain to any off-the-shelf, human immunoglobulin G (IgG) or native IgG isolated from serum. No antibody engineering, cloning, or knowledge of the antibody sequence is required. Bispecific antibodies are generated in just hours. By labeling antibodies isolated from tumor-bearing mice, including two syngeneic models, we generated T cell-redirecting autoantibodies (TRAAbs) that act as an effective therapeutic. TRAAbs preferentially bind tumor tissue over healthy tissue, indicating a previously unexplored therapeutic window. The use of autoantibodies to direct the tumor targeting of bispecific antibodies represents a new paradigm in personalized medicine that eliminates the need to identify tumor biomarkers.
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1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
Sci Adv
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos