Autolus Limited

Ucl Business Plc

Simon Thomas

Martin Pulé

Shaun Cordoba

Shimobi Onuoha

Matteo Righi

Mathieu Ferrari

James Sillibourne

Biao Ma

Wen Chean Lim

Evangelia Kokalaki

John Anderson

Ram Jha

Khai Kong

Maria Stavrou

Vania Baldan

Anna Bulek

Evangelina Kokalaki

The present invention provides a chimeric antigen receptor (CAR) which binds a low density target antigen, which comprises a Fab antigen binding domain. The invention also relates to cells expressing such a CAR and their use in the treatment of disease.

Cytolytic immune cell comprising BCMA- and CD19-specific chimeric antigen receptors

The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising an antigen-binding domain, wherein the antigen-binding domain of the first CAR binds to CD19 and the antigen-binding domain of the second CAR binds to CD22.

Cell lexpressing two chimeric antigen receptors (CARs) at the cell surface

The present invention provides a variant antigen-binding domain which comprises at least one mutation in the VH domain compared to a reference antibody and which displays an increased affinity for TRBC2 over the reference antibody. It further provides an antibody, a chimeric antigen receptor (CAR), and a bispecific T-cell engager (BiTE), a cell which comprises said CAR, and a conjugate comprising said variant antigen-binding domain or said antibody. Additionally, it provides medical uses, diagnostic methods and methods of personalised medicine that exploit the products of the invention.

Binding domain

The present invention provides a chimeric antigen receptor (CAR) which specifically binds CD79 as well as a nucleic acid sequence and a vector encoding the CAR. It further provides a cell which expresses the CAR at the cell surface.

CD79-specific chimeric antigen receptor

The present invention provides a chimeric cytokine receptor (CCR) comprising: (i) an exodomain which binds to a ligand selected from a tumour secreted factor, a chemokine and a cell-surface antigen; and (ii) a cytokine receptor endodomain.

Chimeric transmembrane protein comprising antibody dimerization domains and a type I cytokine receptor endodomain, encoding nucleic acids thereof and methods of use thereof

The present invention relates to a cell comprising a chimeric antigen receptor (CAR) and a constitutively active or inducible Signal Transducer and Activator of Transcription (STAT) molecule.

Cell

Chimeric antigen receptor

The present invention provides a chimeric antigen receptor (CAR) which binds a target antigen having a bulky extracellular domain, wherein the CAR comprises a Fab antigen binding domain. The present invention also provides nucleic acid sequences and constructs encoding such a CAR, cells expressing such a CAR and their therapeutic uses.

Provision of a chimeric antigen receptor (CAR) comprising a disialoganglioside (GD2)-binding domain which comprises •a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences: •b) a light chain variable region (VL) having CDRs with the following sequences: T cells expressing such a CAR are useful in the treatment of some cancers.

The present invention provides a chimeric polypeptide comprising: an antigen-binding domain which constitutively binds to an ectodomain of a first chain of a cytokine receptor; a transmembrane domain; and an endodomain from a second chain of the cytokine receptor which chimeric polypeptide, when expressed in a cell, binds to the endogenous first chain of the cytokine receptor causing constitutive cytokine signalling.

Polypeptide

Methods for treating cancer or modulating T cells or NK cells in a subject by administering cells comprising chimeric transmembrane proteins

Methods for treating cancer or modulating T cells or NK cells in a subject with cancer by administering cells comprising chimeric cytokine receptors

The present invention provides a chimeric antigen receptor (CAR) system comprising; (i) a receptor component comprising a antigen binding domain and a first binding domain; and (ii) a signalling component comprising a signalling domain and a second binding domain which binds the single domain binder of the first binding domain of the receptor component wherein either the first or second binding domains comprise a single domain binder, and wherein, binding of the first and second binding domains is disrupted by the presence of an agent, such that in the absence of the agent, the receptor component and the signalling component heterodimerize and binding of the antigen binding domain to antigen results in signalling through the signalling domain; whereas in the presence of the agent, the receptor component and the signalling component do not heterodimerize and binding of the antigen binding domain to antigen does not result in signalling through the signalling domain.

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London, United Kingdom

Simon Thomas