A CD6-targeted antibody-drug conjugate as a potential therapy for T cell-mediated disorders.
JCI Insight
; 8(23)2023 Dec 08.
Article
em En
| MEDLINE
| ID: mdl-37917882
ABSTRACT
The selective targeting of pathogenic T cells is a holy grail in the development of new therapeutics for T cell-mediated disorders, including many autoimmune diseases and graft versus host disease. We describe the development of a CD6-targeted antibody-drug conjugate (CD6-ADC) by conjugating an inactive form of monomethyl auristatin E (MMAE), a potent mitotic toxin, onto a mAb against CD6, an established T cell surface marker. Even though CD6 is present on all T cells, only the activated (pathogenic) T cells vigorously divide and thus are susceptible to the antimitotic MMAE-mediated killing via the CD6-ADC. We found CD6-ADC selectively killed activated proliferating human T cells and antigen-specific mouse T cells in vitro. Furthermore, in vivo, whereas the CD6-ADC had no significant detrimental effect on normal T cells in naive CD6-humanized mice, the same dose of CD6-ADC, but not the controls, efficiently treated 2 preclinical models of autoimmune uveitis and a model of graft versus host disease. These results provide evidence suggesting that CD6-ADC could be further developed as a potential therapeutic agent for the selective elimination of pathogenic T cells and treatment of many T cell-mediated disorders.
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Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Imunoconjugados
/
Doença Enxerto-Hospedeiro
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article