Related Experiment Video

Updated: Feb 14, 2026

Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
08:09

Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope

Published on: March 24, 2017

10.1K

Safety evaluation of a human chimeric monoclonal antibody that recognizes the extracellular loop domain of claudin-2

Yosuke Hashimoto1, Tomoyuki Hata1, Minoru Tada2

  • 1Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
|February 16, 2018
PubMed

Insights

Claudin-2 (CLDN-2) is a potential cancer target. A novel antibody (xi-1A2) targeting CLDN-2 showed promising results in reducing tumor growth without causing significant adverse effects in preclinical models.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Claudin-2 (CLDN-2) is a tight junction protein implicated in cancer progression.
  • CLDN-2 expression in liver and kidney raises safety concerns for targeted therapies.
  • A rat monoclonal antibody (mAb), clone 1A2, targeting CLDN-2 extracellular domains was previously developed.

Purpose of the Study:

  • To evaluate the safety and efficacy of CLDN-2-targeted cancer therapy using the 1A2 mAb as a model.
  • To generate a chimeric IgG1 antibody (xi-1A2) for potential antibody-dependent cellular cytotoxicity (ADCC).

Main Methods:

  • Generated a human-rat chimeric IgG1 antibody (xi-1A2) from clone 1A2.
  • Assessed xi-1A2's ability to activate Fcγ receptor IIIa.
  • Investigated xi-1A2 biodistribution in mice bearing CLDN-2-expressing fibrosarcoma.
  • Evaluated tumor growth and potential adverse effects following xi-1A2 treatment.

Main Results:

  • Xi-1A2 demonstrated Fcγ receptor IIIa activation in the presence of CLDN-2-expressing cells, suggesting ADCC potential.
  • Intravenous injection of xi-1A2 led to its distribution in liver, kidney, and tumor tissues.
  • Treatment with xi-1A2 significantly attenuated tumor growth in xenografted mice.
  • No apparent adverse effects were observed, including changes in body weight or liver/kidney injury markers.

Conclusions:

  • Xi-1A2 is a promising candidate for safe CLDN-2-targeted cancer therapy.
  • The study supports CLDN-2 as a viable therapeutic target with acceptable safety profile.
Keywords:
Anti-cancer agentBiodistributionClaudin-2EfficacySafety

More Related Videos

Using Reference Reagents to Confirm Robustness of Cytokine Release Assays for the Prediction of Monoclonal Antibody Safety06:37

Using Reference Reagents to Confirm Robustness of Cytokine Release Assays for the Prediction of Monoclonal Antibody Safety

Published on: September 15, 2023

1.2K
Enrichment and Purging of Human Embryonic Stem Cells by Detection of Cell Surface Antigens Using the Monoclonal Antibodies TG30 and GCTM-212:43

Enrichment and Purging of Human Embryonic Stem Cells by Detection of Cell Surface Antigens Using the Monoclonal Antibodies TG30 and GCTM-2

Published on: December 6, 2013

8.2K

Related Concept Videos

Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
14.7K
Survey Safety01:28

Survey Safety

Surveying near highways, rough terrain, or power lines involves significant risks. Working along highways is particularly dangerous and requires the use of warning signs and flagmen. It is safest to avoid working directly on roads and use offsets whenever possible. When highway work is unavoidable, it must follow all safety guidelines. Surveyors should wear bright clothing, such as orange reflective vests, to ensure visibility to motorists, coworkers, and hunters. In construction zones, wearing...
421
Antibody Structure01:10

Antibody Structure

Overview
Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
65.8K
Three Developmental Domains01:29

Three Developmental Domains

Human development is typically examined across three main domains: physical, cognitive, and socio-emotional. These domains represent the significant areas of change and continuity throughout the lifespan, from infancy to late adulthood.
Physical Development
Physical processes, also known as maturation, encompass the biological changes that occur across an individual's life. These changes begin with genetic inheritance and continue through various stages, including growth in height and weight,...
1.2K
Membrane Domains01:18

Membrane Domains

The membrane domains concentrate specific lipids and proteins at one place within the membrane, which helps in cell signaling, adhesion, and other critical cellular processes. These domains can differ in size, composition, function, and lifespan.
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the...
7.3K
Three-Domain System of Life01:21

Three-Domain System of Life

Ribosomal RNA (rRNA) sequence analysis revealed three distinct groups of cells: eukaryotes, bacteria, and archaea. In 1978, Carl R. Woese proposed the concept of domains, a taxonomic level above kingdoms, to differentiate these groups. He suggested that archaea and bacteria, despite their similar appearance, represent separate domains. Domains differ in rRNA, membrane lipid structure, transfer RNA, and antibiotic sensitivity.In this classification, animals, plants, and fungi belong to the...
1.5K