Human derived dimerization tag enhances tumor killing potency of a T-cell engaging bispecific antibody. Academic Article uri icon

Overview

abstract

  • Bispecific antibodies (BsAbs) have proven highly efficient T cell recruiters for cancer immunotherapy by virtue of one tumor antigen-reactive single chain variable fragment (scFv) and another that binds CD3. In order to enhance the antitumor potency of these tandem scFv BsAbs (tsc-BsAbs), we exploited the dimerization domain of the human transcription factor HNF1α to enhance the avidity of a tsc-BsAb to the tumor antigen disialoganglioside GD2 while maintaining functional monovalency to CD3 to limit potential toxicity. The dimeric tsc-BsAb showed increased avidity to GD2, enhanced T cell mediated killing of neuroblastoma and melanoma cell lines in vitro (32-37 fold), exhibited a near 4-fold improvement in serum half-life, and enhanced tumor ablation in mouse xenograft models. We propose that the use of this HNF1α-derived dimerization tag may be a novel and effective strategy to increase the potency of T-cell engaging antibodies for clinical cancer immunotherapy.

publication date

  • April 27, 2015

Identity

PubMed Central ID

  • PMC4485828

Scopus Document Identifier

  • 17344363384

Digital Object Identifier (DOI)

  • 10.1021/ja9733649

PubMed ID

  • 26137406

Additional Document Info

volume

  • 4

issue

  • 4