Autolus Limited

Ucl Business Plc

Shaun Cordoba

Martin Pulé

Simon Thomas

Shimobi Onuoha

Matteo Righi

James Sillibourne

Mathieu Ferrari

Khai Kong

Biao Ma

Wen Chean Lim

Evangelia Kokalaki

Ram Jha

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.

The present invention provides a nucleic acid construct comprising: a first nucleotide sequence of interest (NOI1); a frame-slip motif or a translational readthrough motif (FSM/TRM); and a second nucleotide sequence of interest (NOI2). The invention also provides vectors and cells expressing such a construct. The invention also provides a method for modulating the relative expression of two transgenes in a nucleic acid construct which comprises the step of including a frame-slip motif or a translational readthrough motif between the two transgenes in order to reduce the expression of the downstream transgene.

Nucleic acid construct

The present invention provides a kit of vectors for transducing an immune cell with multiple transgenes comprising: (i) a first vector which comprises a first transgene and a nucleotide sequence encoding a transcription factor and; and (ii) a second vector which comprises a second transgene wherein expression of the second transgene within a host cell is dependent upon expression of the transcription factor.

CAR T-cells comprising transcriptional circuits

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

The present invention provides a nucleic acid construct comprising the following structure: A-X-B in which A is nucleic acid sequence encoding a first polypeptide which comprises a first signal peptide; B is nucleic acid sequence encoding a second polypeptide which comprises a second signal peptide and X is a nucleic acid sequence which encodes a cleavage site, wherein the first signal peptide or the second signal peptide comprises one or more mutation(s) such that it has fewer hydrophobic amino acids.

The present invention provides a nucleic acid construct comprising the following structure: A-X-B in which A and B are nucleic acid sequences encoding a first and a second polypeptide of interest (POI); and X is a nucleic acid sequence which encodes a cleavage site, wherein either the first or second POI is a transmembrane protein which comprises an intracellular retention signal.

Growing community of inventors

London, United Kingdom

Shaun Cordoba