Dataset Information

Conversion of anti-tissue factor antibody sequences to chimeric antigen receptor and bi-specific T-cell engager format.

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.

SUBMITTER: Saunderson SC

PROVIDER: S-EPMC11303627 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Conversion of anti-tissue factor antibody sequences to chimeric antigen receptor and bi-specific T-cell engager format.

Saunderson S C SC Halpin J C JC Tan G M Y GMY Shrivastava P P McLellan A D AD

Cancer immunology, immunotherapy : CII 20240806 10

<h4>Background</h4>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 facto ...[more]

PMID: 39105809

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Dataset Information

Conversion of anti-tissue factor antibody sequences to chimeric antigen receptor and bi-specific T-cell engager format.

Background

Methods

Results

Conclusion

Publications

Conversion of anti-tissue factor antibody sequences to chimeric antigen receptor and bi-specific T-cell engager format.

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