Conditional agonists of immune responses
AssigneeF-star Beta Limited
InventorsMihriban Tuna, John Soerensen Haurum, Jacqueline Francoise Doody, Haijun Sun, Miguel Gaspar
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Abstract
The application relates to antibody molecules, which bind to a first and second antigen, the first antigen being a disease antigen, for example a tumour antigen, and the second antigen being a tumour necrosis factor receptor superfamily (TNFRSF) receptor antigen on the surface of an immune cell. The antibody molecules preferably comprise a CDR-based antigen-binding site and an antigen-binding site, which may be located in two or more structural loops of a constant domain of the antibody molecule. The antibody molecules find application, for example, in cancer therapy.
Claims42
An antibody molecule, which binds to a first antigen and a second antigen, the antibody molecule comprising:
- (i) a CDR-based antigen-binding site for the first antigen;
- and
- (ii) an antigen-binding site for the second antigen located in a constant domain of the antibody molecule, wherein said antigen-binding site comprises one or more amino acid modifications in one or more structural loops of the constant domain;
- and
- wherein one of the first and second antigens is a tumour antigen and the other is a tumour necrosis factor receptor superfamily (TNFRSF) receptor on the surface of an immune cell.
The antibody molecule according to any one of the preceding claims wherein the first antigen is a tumour antigen and the second antigen is a TNFRSF receptor on the surface of an immune cell.
The antibody molecule according to any one of the preceding claims wherein the first antigen is a TNFRSF receptor on the surface of an immune cell and the second antigen is a tumour antigen.
The antibody molecule according to any one of the preceding claims, wherein the TNFRSF receptor expressed on the immune cell requires clustering of three or more receptors for activation.
The antibody molecule according to any one of the preceding claims, wherein the TNFRSF receptor is selected from the group consisting of CD27, EDA2R, EDAR, FAS, LTBR, RELT, TNFRSF1A, TNFRSF1B, TNFRSF6B, TNFRSF8, TNFRSF10A-10D, TNFRSF11A, TNFRSF11B, TNFRSF12A, TNFRSF13B, TNFRSF13C, TNFRSF14, TNFRSF17, TNFRSF18, TNFRSF19, TNFRSF21 and TNFRSF25.
The antibody molecule according to any one of the preceding claims, wherein the immune cell is a T cell.
The antibody molecule according to any one of the preceding claims, wherein the tumour antigen is a cell surface antigen on a cancer cell.
The antibody molecule according to any one of the preceding claims wherein the antibody molecule is a whole antibody.
The antibody molecule according to any one of the preceding claims wherein the antibody molecule does not bind to Fc γ receptors.
The antibody molecule according to any one of the preceding claims wherein the antibody molecule has been modified to reduce or abrogate binding of the CH2 domain of the antibody molecule to one or more Fc γ receptors.
The antibody molecule according to any one of the preceding claims wherein the antibody molecule has one or more antigen-binding sites for the second antigen in the constant region.
The antibody molecule according to any one of the preceding claims, wherein the constant domain is selected from the group consisting of CH3, CH2, CH1 and CL.
The antibody molecule according to any one of the preceding claims, wherein the amino acid modification is an amino acid substitution, addition, or deletion.
The antibody molecule according to any one of the preceding claims, wherein the antigen-binding site for the second antigen comprises one or more amino acid modifications in two or more structural loops of the constant domain.
The antibody molecule according to any one of the preceding claims, wherein the CDR-based antigen binding site for the first antigen comprises three VH domain CDRs and three VL domain CDRs.
The antibody molecule according to any one of the preceding claims wherein the antibody molecule has two CDR-based antigen binding domains for the first antigen.
Dependencies are inferred from the claim text.