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B7-h7-binding agents and methods of use thereof

A B7-H7 and binding agent technology, applied in the field of antibodies binding to human B7-H7 and compositions containing B7-H7 binding agents, which can solve the problem of uninhibited tumor growth and other issues

Pending Publication Date: 2021-06-08
NGM BIOPHARMLS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it is clear that many cancer cells have developed mechanisms to evade the immune system, which can allow unchecked tumor growth

Method used

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  • B7-h7-binding agents and methods of use thereof
  • B7-h7-binding agents and methods of use thereof
  • B7-h7-binding agents and methods of use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0299] B7-H7 expression

[0300] Information from the publicly available database The Cancer Genome Atlas (TCGA) was analyzed to assess B7-H7 mRNA expression in some human cancers and normal tissues. Data from TCGA showed that B7-H7(HHLA2) mRNA was expressed in tissues from cervical, colon, lung, pancreatic, renal, esophageal and gastric cancers ( figure 1 ). In addition, B7-H7 expression was observed in normal colon tissue and very low levels of B7-H7 expression in stomach and pancreas.

Embodiment 2

[0302] Generation of anti-B7-H7 antibodies

[0303] Anti-B7-H7 antibodies were generated using the extracellular domain of human B7-H7 as an immunogen. Recombinant constructs containing the extracellular region of human B7-H7 (aa 23-344) and human Fc sequences were generated and the fusion protein was expressed in mammalian cells. Mice were immunized with B7-H7-Fc protein and boosted several times to induce high titers. Blood was drawn from the immunized mice and antibody titers were determined by ELISA and FACS. Single cell suspensions of lymphocytes were obtained from the spleens and lymph nodes of immunized mice that had been determined to have appropriately high antibody titers. Lymphocytes were fused with murine myeloma cells by standard methods. Cells were dispersed into 96-well plates in selective medium containing HAT.

Embodiment 3

[0305] Antibody screening

[0306] An ELISA assay was used to screen for antibodies that bind to human B7-H7. Binding of antibodies that bind to human B7-H7 to human B7-H7 and cyno B7-H7 expressed on HEK-293T cells was determined by ELISA by FACS. Representative results are shown in Table 10.

[0307] Table 10

[0308]

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Abstract

The present disclosure provides binding agents, such as antibodies, that specifically bind B7-H7, including human B7-H7, as well as compositions comprising the binding agents and methods of their use. The disclosure also provides related polynucleotides and vectors encoding the binding agents and cells comprising the binding agents.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims the benefit of priority from US Provisional Application No. 62 / 720,708, filed on August 21, 2018, the contents of which are incorporated herein in their entirety. [0003] sequence listing [0004] This specification is submitted with a computer readable form (CRF) copy of the Sequence Listing. The CRF titled 47702-0013WO1_SL.txt was created on August 20, 2019, is 110,754 bytes in size, is identical to the paper copy of the Sequence Listing, and is incorporated herein by reference in its entirety. technical field [0005] The present disclosure generally relates to agents that bind B7-H7, particularly antibodies that bind human B7-H7, and compositions comprising B7-H7 binding agents, and methods of treatment using the agents and compositions. Background technique [0006] The basis of immunotherapy is the manipulation and / or regulation of the immune system, including innate and adaptive immune ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28A61K39/00A61P35/00
CPCA61K2039/505A61P35/00C07K16/2827C07K2317/24C07K2317/73C07K2317/76C07K2317/90C07K2317/92A61K45/06
Inventor 许哲源苏珊妮·克里斯汀·克劳利
Owner NGM BIOPHARMLS
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