Virus encoding an anti-TCR-complex antibody or fragment
Inventors
BROWN, Alice Claire Noel • CHAMPION, BRIAN ROBERT
Assignees
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Publication Number
US-11155622-B2
Publication Date
2021-10-26
Expiration Date
Abstract
The present disclosure relates to a replication deficient oncolytic viral vector or replication capable oncolytic virus encoding an antibody or a binding fragment thereof to the antigen-specific T-cell receptor complex (TCR) for expression on the surface of a cancer cell, pharmaceutical compositions comprising the same, and use of any one of the same in treatment, particularly in the treatment of cancer.
Core Innovation
The invention provides a replication deficient oncolytic viral vector or replication capable oncolytic virus for use in cancer, where the virus comprises a first transgene encoding an anti-TCR antibody or a binding fragment thereof and a transmembrane domain or a GPI anchor. The expressed product is displayed on the surface of a cancer cell for in vivo stimulation of T cells.
The viral construct additionally comprises at least one further transgene, and the genes are linked by a 2A peptide. The transgenes are encoded as a polycistronic mRNA, and the virus is specified to be not an adenovirus.
The documented embodiments further describe membrane-anchored anti-CD3ε ScFv constructs linked via P2A to CD80, with related constructs tested in HSV-1 and vaccinia virus. The constructs are described as producing tumor-cell-selective membrane-associated transgene expression that supports T-cell activation.
Claims Coverage
The independent claim set covers three main inventive features: a surface-displayed anti-TCR antibody or binding fragment fused to a transmembrane domain or GPI anchor, 2A-linked polycistronic mRNA cassette expression, and at least one further transgene, with the explicit limitation that the virus is not an adenovirus.
Anti-TCR surface expression with transmembrane domain or GPI anchor
A replication deficient oncolytic viral vector or replication capable oncolytic virus comprising a first transgene encoding an anti-TCR antibody or a binding fragment thereof and a transmembrane domain or a GPI anchor, for expression on the surface of a cancer cell for in vivo stimulation of T cells.
2A-linked polycistronic mRNA cassette architecture
A 2A peptide links said genes, wherein the transgenes are in a cassette encoded as a polycistronic mRNA.
Combination with at least one further transgene
At least one further transgene is included in the replication deficient oncolytic viral vector or replication capable oncolytic virus.
Non-adenovirus oncolytic viral vector
The virus is not an adenovirus.
Coverage centers on an oncolytic viral construct that displays an anti-TCR antibody or binding fragment on the cancer-cell surface using a transmembrane domain or GPI anchor, while using a 2A-linked polycistronic mRNA cassette to co-express additional transgenes, with the constraint that the virus is not an adenovirus.
Stated Advantages
Enhanced in vivo T-cell stimulation.
Documented Applications
In vivo stimulation of T cells by expressing an anti-TCR antibody or binding fragment on the surface of cancer cells using a replication deficient oncolytic viral vector or replication capable oncolytic virus.
Cancer use.
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