RECRUIT-TandAbs: harnessing the immune system to kill cancer cells

Future Oncol. 2012 Jun;8(6):687-95. doi: 10.2217/fon.12.54.

Abstract

Tandem diabodies (TandAbs) are tetravalent bispecific molecules comprised of antibody variable domains with two binding sites for each antigen. RECRUIT-TandAbs can simultaneously engage an immune system effector cell, such as a natural killer cell or a cytotoxic T cell, and an antigen expressed specifically on a cancer cell, thus leading to killing of the cancer cell. Recruitment of immune effector cells is highly specific and mediated via binding of the TandAb to molecules expressed on the surface of these cells. Furthermore, the absence of an Fc domain allows TandAbs to avoid certain IgG-mediated side effects. With a molecular weight of approximately 110 kDa, TandAbs are far above the first-pass renal clearance limit, offering a pharmacokinetic advantage compared with smaller bispecific antibody formats. This article reviews the RECRUIT-TandAb technology and the therapeutic potential of these molecules.

Publication types

  • Review

MeSH terms

  • Antibodies, Bispecific / immunology*
  • Antibodies, Bispecific / metabolism
  • Antibodies, Bispecific / therapeutic use*
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Antigens, CD19 / immunology
  • Antigens, CD19 / metabolism
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • Humans
  • Immunoglobulin Variable Region / chemistry
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / immunology
  • Ki-1 Antigen / immunology
  • Ki-1 Antigen / metabolism
  • Killer Cells, Natural / immunology
  • Neoplasms / drug therapy*
  • Neoplasms / immunology*
  • Peptides / immunology
  • Peptides / metabolism
  • Peptides / therapeutic use
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antibodies, Bispecific
  • Antigens, CD19
  • CD3 Complex
  • Immunoglobulin Variable Region
  • Ki-1 Antigen
  • Peptides