Conversion of anti-tissue factor antibody sequences to chimeric antigen receptor and bi-specific T-cell engager format.
Cancer Immunol Immunother
; 73(10): 195, 2024 Aug 06.
Article
en En
| MEDLINE
| ID: mdl-39105809
ABSTRACT
BACKGROUND:
The efficacy of antibody-targeted therapy of solid cancers is limited by the lack of consistent tumour-associated antigen expression. However, tumour-associated antigens shared with non-malignant cells may still be targeted using conditionally activated-antibodies, or by chimeric antigen receptor (CAR) T cells or CAR NK cells activated either by the tumour microenvironment or following 'unlocking' via multiple antigen-recognition. In this study, we have focused on tissue factor (TF; CD142), a type I membrane protein present on a range of solid tumours as a basis for future development of conditionally-activated BiTE or CAR T cells. TF is frequently upregulated on multiple solid tumours providing a selective advantage for growth, immune evasion and metastasis, as well as contributing to the pathology of thrombosis via the extrinsic coagulation pathway.METHODS:
Two well-characterised anti-TF monoclonal antibodies (mAb) were cloned into expression or transposon vectors to produce single chain (scFv) BiTE for assessment as CAR and CD28-CD3-based CAR or CD3-based BiTE. The affinities of both scFv formats for TF were determined by surface plasmon resonance. Jurkat cell line-based assays were used to confirm the activity of the BiTE or CAR constructs.RESULTS:
The anti-TF mAb hATR-5 and TF8-5G9 mAb were shown to maintain their nanomolar affinities following conversion into a single chain (scFv) format and could be utilised as CD28-CD3-based CAR or CD3-based BiTE format.CONCLUSION:
Because of the broad expression of TF on a range of solid cancers, anti-TF antibody formats provide a useful addition for the development of conditionally activated biologics for antibody and cellular-based therapy.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tromboplastina
/
Linfocitos T
/
Receptores Quiméricos de Antígenos
Límite:
Humans
Idioma:
En
Revista:
Cancer Immunol Immunother
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
NEOPLASIAS
/
TERAPEUTICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Nueva Zelanda