High affinity monoclonal antibodies targeting glypican-2 and uses thereof

A monoclonal antibody, phosphatidylinositol technology, applied in the direction of antibodies, immunoglobulins, antibody medical components, etc., can solve the problem of lack of tumor-specific targets

Pending Publication Date: 2021-03-30
UNITED STATES OF AMERICA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] One of the most difficult challenges in treating neuroblastoma and other deadly solid tumors is the lack of tumor-specific targets

Method used

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  • High affinity monoclonal antibodies targeting glypican-2 and uses thereof
  • High affinity monoclonal antibodies targeting glypican-2 and uses thereof
  • High affinity monoclonal antibodies targeting glypican-2 and uses thereof

Examples

Experimental program
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Embodiment 1

[0357] Example 1: Isolation and characterization of high-affinity GPC2-specific antibodies

[0358] Isolation of GPC2-specific monoclonal antibodies using mouse hybridoma technology. For immunization, a 50-mer peptide (residues 504-553) corresponding to the C-terminus of the cell surface protein GPC2 was synthesized. An additional cysteine ​​residue was introduced at the N-terminus of the peptide. Therefore, it is believed that monoclonal antibodies (mAb) raised against this peptide bind to the C-terminus of membrane-bound GPC2. Three C57BL / 6 mice were immunized 3 times and boosted with peptide-KLH conjugates. Splenocyte fusion was performed using the two best mice. Two antibodies, CT3 and CT5, were isolated in ten clones and were isotyped to IgG1κ. The nucleotide and amino acid sequences of the VH and VL domains of CT3 and CT5 are set forth herein as SEQ ID NOs: 1-8. The positions of the CDR sequences in each domain are shown in Tables 1-4 (see Section III above).

[03...

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Abstract

Monoclonal antibodies that bind glypican-2 (GPC2) with high affinity are described. Immunotoxins and chimeric antigen receptors (CARs) that include the disclosed antibodies or antigen-binding fragments thereof are further described. In some instances, the antibody or antigen-binding fragment is humanized. The disclosed GPC2-specific antibodies and conjugates can be used, for example, for the diagnosis or treatment of GPC2-positive cancers, including neuroblastoma, medulloblastoma and retinoblastoma.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Application No. 62 / 716,169, filed August 8, 2018, which is incorporated herein by reference in its entirety. technical field [0003] The present disclosure relates to monoclonal antibodies that specifically bind Glypican-2 and uses thereof, eg, for the treatment of pediatric cancers. [0004] Thanks for government support [0005] This invention was made with government support under Grant No. Z01 BC010891 awarded by the National Institutes of Health. The government has certain rights in this invention. Background technique [0006] Neuroblastoma is the most common extracranial solid tumor in children. It arises from the neuroendocrine tissue of the sympathetic nervous system and accounts for 8-10% of childhood cancers in the United States (Maris and Hogarty, Lancet 369:2106-2120, 2007). Neuroblastoma is a complex heterogeneous disease, and even with intensi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/18C07K16/30A61K39/00A61K47/68C07K14/725
CPCC07K16/18C07K16/3053C07K2317/24C07K2317/569A61K47/6851C07K2317/21C07K2317/73C07K2317/53C07K14/7051A61K2239/47A61K2239/38A61K39/4631A61K39/4611A61K2239/31A61K39/464474A61K47/6829A61P35/00A61K2039/505C07K16/30C12N15/86G01N33/5748
Inventor 何苗壮B·D·弗莱明李楠
Owner UNITED STATES OF AMERICA
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