A33 antibody compositions and methods of using the same in radioimmunotherapy

An antibody and immunoglobulin technology, which can be used in in vivo radioactive preparations, antibody mimics/scaffolds, preparations for in vivo experiments, etc., and can solve the problems of limited anti-tumor effect and dose escalation.

Pending Publication Date: 2020-07-03
MEMORIAL SLOAN KETTERING CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Furthermore, dose escalation is not feasible due to bystander toxicity in

Method used

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  • A33 antibody compositions and methods of using the same in radioimmunotherapy
  • A33 antibody compositions and methods of using the same in radioimmunotherapy
  • A33 antibody compositions and methods of using the same in radioimmunotherapy

Examples

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preparation example Construction

[0180] Preparation of polyclonal antisera and immunogens. Methods of producing antibodies or antibody fragments of the present technology generally comprise immunizing a subject (usually a non-human subject such as a mouse or rabbit) with purified A33 protein or fragment thereof or with cells expressing the A33 protein or fragment thereof . Suitable immunogenic preparations may contain, for example, recombinantly expressed A33 protein or chemically synthesized A33 peptide. Using standard techniques for polyclonal and monoclonal antibody preparation, the ECM of the A33 protein, or a portion or fragment thereof, can be used as an immunogen to generate anti-A33 antibodies that bind to the A33 protein, or a portion or fragment thereof.

[0181] The full length A33 protein or a fragment thereof can be used as an immunogen as a fragment. In some embodiments, the A33 fragment comprises at least five to eight consecutive amino acid residues of the amino acid sequence of SEQ ID NO:57, ...

Embodiment 1

[0330] Example 1: Materials and Methods for Producing and Characterizing Anti-A33 Antibodies of the Present Technology

[0331] Cell lines and human leukocytes. Cell lines LS174T, Colo205, SNU-16 and 293T cells were purchased from ATCC (Manassas, VA); SW1222 was from ECACC (Salisbury, UK). All cells were verified by STR typing. Cells were maintained in 10% FBS (Sigma, St. Louis, MO), 0.03% L-glutamine (GibcoLaboratories, Gaithersburg, MD) and Pen / Strep (Gibco Laboratories, Gaithersburg, MD) supplemented with 10% FBS (Sigma, St. Louis, MO). ) in RPMI medium. Buffy coats from healthy donors were purchased from New York Blood Center (New York City, NY) and human PBMCs were isolated by Ficoll gradients of buffy coats.

[0332] Establishment of cell lines expressing luciferase. 293T cells were first transfected with a retroviral construct containing the luciferase and GFP genes using PolyJet transfection reagent (SignaGen, Rockville, MD) according to the manufacturer's instru...

Embodiment 2

[0348] Example 2: Structure and Binding Affinity of Humanized Anti-A33 Antibodies of the Present Technology

[0349] Figure 14 The V of the murine A33 antibody is shown H and V L Amino acid sequences of domains and their corresponding homologous human sequences (SEQ ID NO: 1-4). The V of the 3A3-H1 / L1, 3A3-H1 / L2, 3A3-H2 / L1 and 3A3-H2 / L2 humanized A33 antibodies of the present technology H and V L The amino acid sequence of the domain is in Figure 15 and Figure 17 shown in . V of the 3A3-H1 / L1, 3A3-H1 / L2, 3A3-H2 / L1 and 3A3-H2 / L2 humanized A33 antibodies H and V L The cDNA sequence of the domain is in Figure 16 and Figure 18 shown in . Figure 19 An alignment of the original humanized amino acid sequence hA33 from King et al. (1995) supra with the newly rehumanized huA33 (3A3) amino acid sequence is shown.

[0350] Figure 24 The amino acid sequences of the light and heavy chains of chimeric chA33-IgG1 are shown, corresponding to SEQ ID NO: 13 and SEQ ID NO: ...

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Abstract

The present disclosure relates generally to immunoglobulin-related compositions (e.g., antibodies or antigen binding fragments thereof) that can bind to and neutralize the activity of A33 protein. Theantibodies of the present technology are useful in methods for detecting and treating an A33 -positive cancer in a subject in need thereof.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit and priority of U.S. Provisional Patent Application No. 62 / 562,373, filed September 23, 2017, and U.S. Provisional Patent Application No. 62 / 562,374, filed September 23, 2017, the contents of which are hereby incorporated by reference Its entirety is incorporated herein. technical field [0003] The present technology generally relates to the preparation of and uses of immunoglobulin-related compositions (eg, antibodies or antigen-binding fragments thereof) that specifically bind an A33 protein. Specifically, the technology relates to the preparation of A33 neutralizing antibodies and the use of said antibodies in the detection and treatment of A33-related cancers. Background technique [0004] The following description of the technical background of the present technology is provided only to facilitate understanding of the present technology, and it is not admitted that the descrip...

Claims

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Application Information

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IPC IPC(8): A61K31/555A61K39/395A61K45/00A61K47/54A61K51/04A61P35/00
CPCC07K16/2803C07K16/2809A61K2039/505C07K2317/24C07K2317/31C07K2317/52C07K2317/622C07K2317/92C07K2319/00A61P35/00A61K2039/828A61K2039/82A61K51/0482A61K51/109C07K2317/54C07K2317/55C07K2317/565C07K2317/73
Inventor Z·吴H·徐N-K·张
Owner MEMORIAL SLOAN KETTERING CANCER CENT
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