In vivo targeting and growth inhibition of the A20 murine B-cell lymphoma by an idiotype-specific peptide binder.

Abstract

B-cell lymphoma is a clonal expansion of neoplastic cells that may result in fatal outcomes. Here, we report the in vivo targeting and growth inhibition of aggressive A20 murine B-cell lymphoma by idiotype-specific peptide pA20-36. pA20-36 was selected from random peptide libraries and bound specifically to the B-cell receptor (BCR) of A20 cells in mice engrafted with A20 lymphoma, as shown by histology and positron emission tomographic analysis. BCR cross-linking of A20 cells with pA20-36 resulted in massive apoptosis of targeted tumor cells and in an increased survival of the diseased animals without any detectable evidence of toxicity. The pA20-36 treatment reverted the immune suppression of the tumor microenvironment as shown by reduced expression of vascular endothelial growth factor, interleukin-10, and transforming growth factor-beta cytokines together with a lower number of CD11b+Gr-1+ inhibitor myeloid-derived suppressor cells and Foxp3+CD4+ Treg cells. Furthermore, pA20-36 treatment was associated with an increased number of tumor-infiltrating, activated CD8+ T cells that exerted a tumor-specific cytolytic activity. These findings show that a short peptide that binds specifically to the complementarity-determining regions of the A20 BCR allows in vivo detection of neoplastic cells together with significant inhibition of tumor growth in vivo.

• Authors: Camillo Palmieri, Cristina Falcone, Enrico Iaccino, Franca Maria Tuccillo, Marco Gaspari, Francesca Trimboli, Annamaria De Laurentiis, Laura Luberto, Marilena Pontoriero, Antonio Pisano, Eleonora Vecchio, Olga Fierro, Maria Rosaria Panico, Michele Larobina, Sara Gargiulo, Nicola Costa, Fabrizio Dal Piaz, Marco Schiavone, Claudio Arra, Aldo Giudice, Giuseppe Palma, Antonio Barbieri, Ileana Quinto, Giuseppe Scala
• Journal: Blood (Blood) Vol. 116 Issue 2 Pg. 226-38 (Jul 15 2010) ISSN: 1528-0020 [Electronic] United States
• PMID: 20363775 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Anti-Idiotypic
• Antibodies, Monoclonal
• Antineoplastic Agents
• Immunoglobulin Idiotypes
• Peptide Library
• Peptides
• Receptors, Antigen, B-Cell

Topics

• Animals
• Antibodies, Anti-Idiotypic (immunology, therapeutic use)
• Antibodies, Monoclonal (immunology, therapeutic use)
• Antibody Specificity
• Antineoplastic Agents (therapeutic use)
• Cell Line, Tumor
• Cell Proliferation
• Cell Separation
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Immunoglobulin Idiotypes (immunology)
• Immunotherapy (methods)
• Lymphoma, B-Cell (immunology, therapy)
• Mice
• Mice, Inbred BALB C
• Microscopy, Confocal
• Peptide Library
• Peptides (immunology, therapeutic use)
• Positron-Emission Tomography
• Receptors, Antigen, B-Cell (immunology)
• Surface Plasmon Resonance