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Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction
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An antibody-supermolecule conjugate for tumor-specific targeting of tumoricidal methylated β-cyclodextrin-threaded

Kei Nishida1, Astushi Tamura, Tae Woong Kang

  • 1Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), Chiyoda, 2-3-10 Kanda-Surugadai, Tokyo 101-0062, Japan. tamura.org@tmd.ac.jp.

Journal of Materials Chemistry. B
|June 24, 2020
PubMed

Insights

New antibody-drug conjugates target HER2-expressing tumors. These conjugates deliver methylated β-cyclodextrin (Me-PRX) to induce cancer cell death, offering a promising approach for chemotherapy.

Area of Science:

  • Biomedical Engineering
  • Cancer Research
  • Drug Delivery Systems

Background:

  • Methylated β-cyclodextrin-containing polyrotaxane (Me-PRX) induces endoplasmic reticulum (ER) stress and autophagic cell death, effective even in apoptosis-resistant cancer cells.
  • Targeted delivery of Me-PRX to tumors is crucial for effective cancer treatment.

Purpose of the Study:

  • To design and evaluate antibody-supermolecule conjugates for targeted delivery of Me-PRX to HER2-expressing tumors.
  • To assess the efficacy of these conjugates in reducing tumor cell viability.

Main Methods:

  • Conjugation of phenyl maleimide group-modified Me-PRX (Mal-Me-PRX) to Trastuzumab, an anti-HER2 antibody, creating Trastuzumab-Me-PRX (Tras-Me-PRX).
  • Evaluation of cellular association of Tras-Me-PRX with HER2-expressing tumor cells.
  • Assessment of Tras-Me-PRX's effect on tumor cell viability compared to unmodified Me-PRX.

Main Results:

  • Tras-Me-PRX showed significantly greater cellular association with HER2-expressing tumor cells compared to unmodified Me-PRX.
  • Tras-Me-PRX demonstrated enhanced efficacy in reducing the viability of HER2-expressing tumor cells at lower concentrations.
  • The conjugate effectively targeted and inhibited tumor cell growth.

Conclusions:

  • Antibody-Me-PRX conjugates represent a novel class of antibody-drug conjugates for cancer therapy.
  • Tras-Me-PRX exhibits potent anti-tumor activity through targeted delivery of Me-PRX.
  • This approach holds potential for improving chemotherapy outcomes in HER2-positive cancers.

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