Heterodimeric bispecific single-chain variable-fragment antibodies against EpCAM and CD16 induce effective antibody-dependent cellular cytotoxicity against human carcinoma cells

Daniel A. Vallera, Bin Zhang, Michelle K. Gleason, Seunguk Oh, Louis M. Weiner, Dan S. Kaufman, Valarie Mccullar, Jeffrey S. Miller, Michael R. Verneris

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

A heterodimeric bispecific biological recombinant drug was synthesized by splicing DNA fragments from two fully humanized single-chain variable-fragment (scFV) antibody fragments forming a novel drug simultaneously recognizing the CD16 natural killer (NK) cell marker and the cancer marker epithelial cell adhesion molecule (EpCAM). The drug precipitously enhanced the killing of human carcinomas of the prostate, breast, colon, head, and neck even at very low effector:target ratios. The drug EpCAM16 rendered even nonactivated NK cell-proficient killers and activated them to kill via degranulation and cytokine production. Studies show that bispecific antibodies can be used to induce proficient killing of the carcinoma targets that ordinarily are resistant to NK-mediated killing. Apparently, the innate immune system can be effectively recruited to kill cancer cells using the bispecific antibody platform and EpCAM targeting.

Original languageEnglish (US)
Pages (from-to)274-282
Number of pages9
JournalCancer Biotherapy and Radiopharmaceuticals
Volume28
Issue number4
DOIs
StatePublished - May 1 2013

Keywords

  • ADCC
  • Anti-CD16
  • Bispecific antibody
  • Carcinoma
  • Human NK cells

Fingerprint Dive into the research topics of 'Heterodimeric bispecific single-chain variable-fragment antibodies against EpCAM and CD16 induce effective antibody-dependent cellular cytotoxicity against human carcinoma cells'. Together they form a unique fingerprint.

Cite this