Targeting lymphoma with precision using semisynthetic anti-idiotype peptibodies

Proc Natl Acad Sci U S A. 2016 May 10;113(19):5376-81. doi: 10.1073/pnas.1603335113. Epub 2016 Apr 25.


B-cell lymphomas express a functionally active and truly tumor-specific cell-surface product, the variable region of the B-cell receptor (BCR), otherwise known as idiotype. The tumor idiotype differs, however, from patient to patient, making it a technical challenge to exploit for therapy. We have developed a method of targeting idiotype by using a semisynthetic personalized therapeutic that is more practical to produce on a patient-by-patient basis than monoclonal antibodies. In this method, a small peptide with affinity for a tumor idiotype is identified by screening a library, chemically synthesized, and then affixed to the amino terminus of a premade IgG Fc protein. We demonstrate that the resultant semisynthetic anti-idiotype peptibodies kill tumor cells in vitro with specificity, trigger tumor cell phagocytosis by macrophages, and efficiently clear human lymphoma in a murine xenograft model. This method could be used to target tumor with true precision on a personalized basis.

Keywords: idiotype; lymphoma; peptibody; precision medicine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / administration & dosage*
  • Antibodies, Anti-Idiotypic / immunology
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / immunology
  • Drug Design
  • Female
  • Humans
  • Lymphoma / immunology*
  • Lymphoma / pathology
  • Lymphoma / therapy*
  • Mice
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Protein Engineering / methods*
  • Recombinant Fusion Proteins / administration & dosage
  • Treatment Outcome
  • Tumor Cells, Cultured
  • Vaccines, Synthetic / administration & dosage*
  • Vaccines, Synthetic / immunology


  • Antibodies, Anti-Idiotypic
  • Cancer Vaccines
  • Recombinant Fusion Proteins
  • Vaccines, Synthetic