Targeted desialylation and cytolysis of tumour cells by fusing a sialidase to a bispecific T-cell engager.
Nat Biomed Eng
; 8(5): 499-512, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38693431
ABSTRACT
Bispecific T-cell engagers (BiTEs) bring together tumour cells and cytotoxic T cells by binding to specific cell-surface tumour antigens and T-cell receptors, and have been clinically successful for the treatment of B-cell malignancies. Here we show that a BiTE-sialidase fusion protein enhances the susceptibility of solid tumours to BiTE-mediated cytolysis of tumour cells via targeted desialylation-that is, the removal of terminal sialic acid residues on glycans-at the BiTE-induced T-cell-tumour-cell interface. In xenograft and syngeneic mouse models of leukaemia and of melanoma and breast cancer, and compared with the parental BiTE molecules, targeted desialylation via the BiTE-sialidase fusion proteins enhanced the formation of immunological synapses, T-cell activation and T-cell-mediated tumour-cell cytolysis in the presence of the target antigen. The targeted desialylation of tumour cells may enhance the potency of therapies relying on T-cell engagers.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neuraminidase
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Nat Biomed Eng
Year:
2024
Document type:
Article
Affiliation country:
Publication country:
ENGLAND
/
ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
/
REINO UNIDO
/
SCOTLAND
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UK
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UNITED KINGDOM