Biomolecular engineering of antidehydroepiandrosterone antibodies: a new perspective in cancer diagnosis and treatment using single-chain antibody variable fragment

Nanomedicine (Lond). 2019 Mar;14(6):689-705. doi: 10.2217/nnm-2018-0230. Epub 2019 Jan 29.

Abstract

Aim: To develop a monoclonal antibody against dehydroepiandrosterone (DHEA) and miniaturize it, generating a single-chain antibody variable fragment (scFv) against DHEA as an adrenocortical carcinoma (ACC) marker.

Material & methods: DHEA conjugated to keyhole limpet hemocyanin was used as an immunogen to obtain anti-DHEA hybridomas. Variable fragments were cloned from hybridoma 5B7 total RNA, and used to detect DHEA in normal adrenal tissue and ACC cells.

Results: IgM monoclonal antibody was highly specific, and the recombinant scFv preserved parental antibody characteristics, allowing tissue localization of DHEA.

Conclusion: Undefined small lesions are challenges for clinicians and impact clinical adrenocortical tumor management. Generating an anti-DHEA scFv facilitates development of imaging tests for early diagnosis of pediatric ACC.

Keywords: DHEA; adrenal cortex; adrenocortical carcinoma; dehydroepiandrosterone; monoclonal antibody; scFv; tumor marker; zona reticularis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Neoplasms / diagnosis*
  • Adrenocortical Carcinoma / diagnosis*
  • Animals
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / metabolism
  • Dehydroepiandrosterone / analysis*
  • Dehydroepiandrosterone / metabolism
  • Gene Expression
  • Humans
  • Mice, Inbred BALB C
  • Molecular Docking Simulation
  • Protein Conformation
  • Protein Engineering / methods
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Single-Chain Antibodies / genetics
  • Single-Chain Antibodies / metabolism*
  • Zona Reticularis / metabolism

Substances

  • Biomarkers, Tumor
  • Recombinant Proteins
  • Single-Chain Antibodies
  • Dehydroepiandrosterone