A vaccine directed to B cells and produced by cell-free protein synthesis generates potent antilymphoma immunity

Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14526-31. doi: 10.1073/pnas.1211018109. Epub 2012 Aug 8.

Abstract

Clinical studies of idiotype (Id) vaccination in patients with lymphoma have established a correlation between the induced anti-Id antibody responses and favorable clinical outcomes. To streamline the production of an Id vaccine, we engineered a small diabody (Db) molecule containing both a B-cell-targeting moiety (anti-CD19) and a lymphoma Id. This molecule (αCD19-Id) was designed to penetrate lymph nodes and bind to noncognate B cells to form an antigen presentation array. Indeed, the αCD19-Id molecule accumulated on B cells in vivo after s.c. administration. These noncognate B cells, decorated with the diabody, could then stimulate the more rare Id-specific B cells. Peptide epitopes present in the diabody linker augmented the response by activating CD4(+) helper T cells. Consequently, the αCD19-Id molecule induced a robust Id-specific antibody response and protected animals from tumor challenge. Such diabodies are produced in a cell-free protein expression system within hours of amplification of the specific Ig genes from the B-cell tumor. This customized product can now be available to vaccinate patients before they receive other, potentially immunosuppressive, therapies.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / immunology*
  • Antigens, CD19 / immunology
  • B-Lymphocytes / immunology*
  • Cancer Vaccines / immunology*
  • DNA Primers / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Escherichia coli
  • Flow Cytometry
  • Immunotherapy / methods*
  • Lymphoma / immunology*
  • Lymphoma / prevention & control*
  • Mice
  • Plasmids / genetics
  • Signal Transduction / immunology*

Substances

  • Antibodies, Anti-Idiotypic
  • Antigens, CD19
  • Cancer Vaccines
  • DNA Primers