Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies

Sci Transl Med. 2015 May 13;7(287):287ra70. doi: 10.1126/scitranslmed.aaa4802.


Bispecific antibodies and antibody fragments in various formats have been explored as a means to recruit cytolytic T cells to kill tumor cells. Encouraging clinical data have been reported with molecules such as the anti-CD19/CD3 bispecific T cell engager (BiTE) blinatumomab. However, the clinical use of many reported T cell-recruiting bispecific modalities is limited by liabilities including unfavorable pharmacokinetics, potential immunogenicity, and manufacturing challenges. We describe a B cell-targeting anti-CD20/CD3 T cell-dependent bispecific antibody (CD20-TDB), which is a full-length, humanized immunoglobulin G1 molecule with near-native antibody architecture constructed using "knobs-into-holes" technology. CD20-TDB is highly active in killing CD20-expressing B cells, including primary patient leukemia and lymphoma cells both in vitro and in vivo. In cynomolgus monkeys, CD20-TDB potently depletes B cells in peripheral blood and lymphoid tissues at a single dose of 1 mg/kg while demonstrating pharmacokinetic properties similar to those of conventional monoclonal antibodies. CD20-TDB also exhibits activity in vitro and in vivo in the presence of competing CD20-targeting antibodies. These data provide rationale for the clinical testing of CD20-TDB for the treatment of CD20-expressing B cell malignancies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific / immunology
  • Antibodies, Bispecific / pharmacokinetics
  • Antibodies, Bispecific / therapeutic use*
  • Antigens, CD20 / immunology*
  • CD3 Complex / immunology*
  • Humans
  • Leukemia, B-Cell / immunology
  • Leukemia, B-Cell / therapy*
  • Macaca fascicularis
  • Mice
  • Mice, Transgenic
  • T-Lymphocytes / immunology*


  • Antibodies, Bispecific
  • Antigens, CD20
  • CD3 Complex