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Macropinocytosis human anti-CD46 antibodies and targeted cancer therapies

An antibody, human technology, applied in the direction of antibodies, chemical instruments and methods, anti-animal/human immunoglobulin, etc., can solve the problem of not providing the degree of specificity of cancer cells

Pending Publication Date: 2022-03-01
RGT UNIV OF CALIFORNIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] Although many antibodies have been discovered by this method, the screening process against cell lines does not provide a picture of how specific these antibodies are to the actual cancer cells in the patient population

Method used

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  • Macropinocytosis human anti-CD46 antibodies and targeted cancer therapies
  • Macropinocytosis human anti-CD46 antibodies and targeted cancer therapies
  • Macropinocytosis human anti-CD46 antibodies and targeted cancer therapies

Examples

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example

[0656] The following examples are offered to illustrate, not limit, the invention.

example 1

[0658] Novel anti-CD46 antibodies and uses thereof

[0659] To identify novel anti-human CD46 antibodies, a recombinant Fc fusion protein consisting of Sushi domains 1 and 2 of human CD46 was formed. Since the complementary sequence elements primarily bind to domains 3 and 4, the selection of domains 1 and 2 minimizes the selection of antibodies that might strongly interfere with standard complementary sequence function. This CD46-Fc fusion was made and purified from transfected HEK293 cells by protein A affinity chromatography. For human antibody selection, pooled cDNA from peripheral blood mononuclear cells of 426 healthy human donors was used to form 5 x 10 9 A phagemid display library of 2 members was selected, and the library was selected for recombinant CD46-Fc fusion proteins. After three rounds of selection, binding phagemids were screened by FACS and sequencing. Meanwhile, an alternative strategy was employed, which involved first selection of the library on live...

example 2

[0681] CD46 ADC is highly active in an intrafemoral mCRPC xenograft model.

[0682] Because more than 95% of prostate cancers metastasize to bone sites, we further investigated the efficacy of our anti-CD46 ADCs in bone xenograft models. We injected the metastatic castration-resistant prostate cancer (mCRPC) cell line LNCaP C4-2B carrying a firefly luciferase reporter into the femur of NSG mice to create an intraskeletal mCRPC xenograft model. Seven days after transplantation, CD46 ADC (YS5-mcvcpab-MMAF) was injected every 4 days for a total of 4 sessions. Tumor status was monitored by bioluminescent imaging during and after treatment. Such as Figure 32 As shown in , CD46 ADC-treated mice showed profound tumor suppression after the treatment period and continued until the end of the experiment (day 65), suggesting that our CD46 ADC is highly effective in this endogenous mCRPC xenograft model.

[0683] CD46 is highly expressed in CRPC and mCRPC tissues.

[0684] In add...

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Abstract

The invention relates to macropinocytosis human anti-CD46 antibodies and targeted cancer therapies. In various embodiments, provided are human anti-CD46 antibodies that internalize via the macropinocytosis pathway and enter tumor cells, as well as antibody-drug conjugates (ADC) developed from these antibodies for diagnostic and / or therapeutic targeting of CD46 over-expressing tumors.

Description

[0001] This application is a divisional application of an invention patent application with an application date of September 10, 2015, an application number of 201580061138.5, and an invention title of "Macropinocytosis of Human Anti-CD46 Antibody and Targeted Cancer Therapy". [0002] Cross References to Related Applications [0003] This application claims the benefit of and priority to USSN 62 / 049,973 filed September 12, 2014, which is hereby incorporated by reference in its entirety for all purposes. [0004] Statement of Rights Concerning Inventions Made Under Federally Sponsored Research and Development [0005] This study was supported in part by grant numbers from The National Institutes of Health: R01 CA118919, R01 CA129491, and R01 CA171315. The government has certain rights in this invention. technical field [0006] The present application relates generally to macropinocytosis of human anti-CD46 antibodies and targeted cancer therapy. Background technique ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28C07K16/30A61K38/07A61K47/68A61P35/00
CPCC07K16/30A61K51/1027C07K16/3069A61K2039/505C07K2317/30A61K31/7088G01N33/57492G01N2333/70596A61K47/6817C07K16/2896A61K47/6849A61P13/08A61P35/00A61P35/04Y02A50/30C07K2317/21A61K47/6811C07K2317/54C07K2317/569C07K2317/56C07K2317/77C07K2317/55A61K47/6869C07K2317/565
Inventor 刘滨苏旸斯科特·比德林梅尔克里斯托弗·R·贝伦斯李南炅
Owner RGT UNIV OF CALIFORNIA
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