Antigen receptors and uses thereof
AssigneesTRON—Translationale Onkologie an der Universitätsmedizin der Johannes Gutenberg-Universität Mainz gemeinnützige GmbH, BioNTech Cell & Gene Therapies GmbH
InventorsRalf Holger Voss, Ugur Sahin, Petra Oehm, Matthias Birtel, Janina Caspar
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Abstract
The present invention generally embraces the treatment of diseases by targeting cells expressing an antigen on the cell surface. In particular the invention relates to recombinant antigen receptors and uses thereof. T cells engineered to express such antigen receptors are useful in the treatment of diseases characterized by expression of one or more antigens bound by the antigen receptors.
Claims15
An antigen receptor, which receptor comprises a first peptide chain and a second peptide chain,
- wherein:
- (i) the first peptide chain comprises an immunoglobulin heavy chain variable domain (VH), an immunoglobulin light chain variable domain (VL), a variable region of a T cell receptor chain, and an immunoreceptor signal transmission domain, and
- the second peptide chain comprises an immunoglobulin heavy chain variable domain (VH), an immunoglobulin light chain variable domain (VL), a variable region of a T cell receptor chain, and an immunoreceptor signal transmission domain, and
- wherein the VH domain from the first peptide chain forms together with the VL domain from the second peptide chain a first antigen binding site, and
- wherein the VL domain from the first peptide chain forms together with the VH domain from the second peptide chain a second antigen binding site;
- or
- (ii) the first peptide chain comprises two immunoglobulin light chain variable domains (VL), a variable region of a T cell receptor chain, and an immunoreceptor signal transmission domain, and
- the second peptide chain comprises two immunoglobulin heavy chain variable domains (VH), a variable region of a T cell receptor chain, and an immunoreceptor signal transmission domain, and
- wherein a first VL domain from the first peptide chain forms a first antigen binding site together with a first VH domain from the second peptide chain, and
- wherein a second VL domain from the first peptide chain forms a second antigen binding site together with a second VH domain from the second peptide chain.
A method for producing a cell expressing an antigen receptor which receptor comprises a first peptide chain and a second peptide chain, the method comprising:
- (A)
- (a) providing a cell;
- (b) providing a first genetic construct, wherein the first genetic construct encodes the first peptide chain comprising
- an immunoglobulin heavy chain variable domain (VH), an immunoglobulin light chain variable domain (VL), a variable region of a T cell receptor chain, and an immunoreceptor signal transmission domain;
- (c) providing a second genetic construct, wherein the second genetic construct encodes the second peptide chain comprising an immunoglobulin heavy chain variable domain (VH), an immunoglobulin light chain variable domain (VL), a variable region of a T cell receptor chain, and an immunoreceptor signal transmission domain;
- (d) introducing the first and second genetic constructs into the cell;
- and
- (e) allowing the constructs to be expressed in the cell,
- wherein the VH domain from the first peptide chain is able to form together with the VL domain from the second peptide chain a first antigen binding site, and wherein the VL domain from the first peptide chain is able to form together with the VH domain from the second peptide chain a second antigen binding site;
- or
- (B)
- (a) providing a cell;
- (b) providing a first genetic construct, wherein the first genetic construct encodes the first peptide chain comprising
- two immunoglobulin light chain variable domains (VL), a variable region of a T cell receptor chain, and an immunoreceptor signal transmission domain;
- (c) providing a second genetic construct, wherein
- the second genetic construct encodes the second peptide chain comprising two immunoglobulin heavy chain variable domains (VH), a variable region of a T cell receptor chain, and an immunoreceptor signal transmission domain;
- (d) introducing the first and second genetic constructs into the cell;
- and
- (e) allowing the constructs to be expressed in the cell;
- wherein a first VL domain from the first peptide chain is able to form a first antigen binding site together with a first VH domain from the second peptide chain, and
- wherein a second VL domain from the first peptide chain is able to form a second antigen binding site together with a second VH domain from the second peptide chain.
A combination of nucleic acids wherein the first nucleic acid encodes a first peptide chain and a second nucleic acid encodes a second peptide chain, or a nucleic acid encoding both a first and a second peptide chain, wherein
- (i) the first peptide chain comprises an immunoglobulin heavy chain variable domain (VH), an immunoglobulin light chain variable domain (VL), a variable region of a T cell receptor chain, and an immunoreceptor signal transmission domain, and
- the second peptide chain comprises an immunoglobulin heavy chain variable domain (VH), an immunoglobulin light chain variable domain (VL), a variable region of a T cell receptor chain, and an immunoreceptor signal transmission domain, and
- wherein the VH domain from the first peptide chain forms together with the VL domain from the second peptide chain a first antigen binding site, and
- wherein the VL domain from the first peptide chain forms together with the VH domain from the second peptide chain a second antigen binding site;
- or
- (ii) the first peptide chain comprises two immunoglobulin light chain variable domains (VL), a variable region of a T cell receptor chain, and an immunoreceptor signal transmission domain, and
- the second peptide chain comprises two immunoglobulin heavy chain variable domains (VH), a variable region of a T cell receptor chain, and an immunoreceptor signal transmission domain;
- and
- wherein a first VL domain from the first peptide chain forms a first antigen binding site together with a first VH domain from the second peptide chain, and
- wherein a second VL domain from the first peptide chain is able to form a second antigen binding site together with a second VH domain from the second peptide chain.
Dependencies are inferred from the claim text.