Multi-specific polypeptide useful for localized tumor immunomodulation
US10927154B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Jan 12, 2015 |
| Grant date | Feb 23, 2021 |
| Priority date | — |
| Expiry date | Jan 12, 2035 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07K2319/30
- WIPO fieldBiotechnology
- WIPO sectorChemistry
Abstract
The disclosure provides a multi-specific polypeptide with a first moiety specific for a tumor-associated antigen on tumor cell surface and a second moiety specific for an immune checkpoint protein, which multi-specific polypeptide can be useful for biasing a T-cell-mediated response to a tumor micro-environment. For example, the polypeptide may contain: a) a first binding domain, for example, a full-length antibody or an antigen-binding domain of an antibody, specifically recognizing a tumor-associated antigen on tumor cell surface, and b) a second binding domain, such as a lipocalin mutein, capable of stimulating T-cell proliferation e.g., by inhibiting a protein receptor that down-regulates the immune system. The first binding domain may be genetically linked (i.e., peptide bond at its N- or C-terminus) to the second binding domain. The multispecific polypeptide also may contain a third or yet additional specific binding moieties, any of which can specifically bind a distinct immune checkpoint protein. The polypeptide may contain an Fc region of an antibody or of an antigen-binding domain thereof and simultaneously engage (1) a T cell receptor complex of a T cell, (2) a tumor-ass…
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