Anti-WT1/HLA bi-specific antibody
US10239952B2 · kind B2 · utility
Assignees
Inventors
Key dates
| Filing date | Nov 7, 2014 |
| Grant date | Mar 26, 2019 |
| Priority date | — |
| Expiry date | Nov 7, 2034 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07K2317/73
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
Disclosed herein is a bi-specific form of a T cell receptor mimic (TCRm) mAb with reactivity to human immune effector cell antigen and a WT1 peptide/HLA-A epitope. This antibody selectively bound to leukemias and solid tumor cells expressing WT1 and HLA-A as well as activated resting human T cells to release interferon-(IFN-γ) and to kill the target cancer cells in vitro. Importantly, the antibody mediated autologous T cell proliferation and directed potent cytotoxicity against fresh ovarian cancer cells. Therapeutic activity in vivo of the antibody was demonstrated in NOD SCID SCID Yc*(NSG) mice with three different human cancers expressing WT1/HLA-A2 including disseminated Ph+ acute lymphocytic leukemia (ALL), disseminated acute myeloid leukemia, and peritoneal mesothelioma. In both of the leukemia xenograft models, mice that received the antibody and T cells also showed longer survival and delayed limb paralysis. Also provided are methods for stimulating a primary T cell response comprising stimulating cytotoxic T cells against a first tumor antigen and a secondary T cell response comprising stimulating effector T cells and/or memory T cells against a first tumor antigen and/or …
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