In vivo targeting and growth inhibition of the A20 murine B-cell lymphoma by an idiotype-specific peptide binder.
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.
Palmieri
Camillo
C
Department of Experimental and Clinical Medicine, University of Catanzaro Magna Graecia, Catanzaro, Italy.
Falcone
Cristina
C
Iaccino
Enrico
E
Tuccillo
Franca Maria
FM
Gaspari
Marco
M
Trimboli
Francesca
F
De Laurentiis
Annamaria
A
Luberto
Laura
L
Pontoriero
Marilena
M
Pisano
Antonio
A
Vecchio
Eleonora
E
Fierro
Olga
O
Panico
Maria Rosaria
MR
Larobina
Michele
M
Gargiulo
Sara
S
Costa
Nicola
N
Dal Piaz
Fabrizio
F
Schiavone
Marco
M
Arra
Claudio
C
Giudice
Aldo
A
Palma
Giuseppe
G
Barbieri
Antonio
A
Quinto
Ileana
I
Scala
Giuseppe
G
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000918:Antibody Specificity; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D019151:Peptide Library; D010455:Peptides / Q000276:immunology* / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D020349:Surface Plasmon Resonance
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007130:Immunoglobulin Idiotypes; D019151:Peptide Library; D010455:Peptides; D011947:Receptors, Antigen, B-Cell