Human derived dimerization tag enhances tumor killing potency of a T-cell engaging bispecific antibody Journal Article


Authors: Ahmed, M.; Cheng, M.; Cheung, I. Y.; Cheung, N. K. V.
Article Title: Human derived dimerization tag enhances tumor killing potency of a T-cell engaging bispecific antibody
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. © 2015 Taylor & Francis Group, LLC.
Keywords: melanoma; immunotherapy; neuroblastoma; t-cell; ganglioside; gd2; bispecific antibody; bite
Journal Title: OncoImmunology
Volume: 4
Issue: 4
ISSN: 2162-4011
Publisher: Landes Bioscience  
Date Published: 2015-04-01
Start Page: e989776
Language: English
DOI: 10.4161/2162402x.2014.989776
PROVIDER: scopus
PMCID: PMC4485828
PUBMED: 26137406
DOI/URL:
Notes: Article -- Export Date: 3 February 2016 -- Source: Scopus
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MSK Authors
  1. Nai-Kong Cheung
    532 Cheung
  2. Irene Y Cheung
    80 Cheung
  3. Mahiuddin Ahmed
    12 Ahmed
  4. Ming Cheng
    6 Cheng