The peptide nucleic acid targeted to a regulatory sequence of the translocated c-myc oncogene in Burkitt's lymphoma lacks immunogenicity: follow-up characterization of PNAEmu-NLS.
The present study aims to evaluate the antigenicity of a PNA complementary to the Emu sequence (PNAEmu) with cancer therapeutic potential properties in Burkitt's lymphoma (BL). In BL cells, the c-myc oncogene is repositioned next to the Emu enhancer of the immunoglobulin (Ig) locus, due to chromosomal translocation, and up-regulated. PNAEmu linked to a nuclear localization signal peptide was shown specifically to block c-myc hyperexpression by inhibiting cell growth in vitro and in vivo. Recently, we reported that the administration of PNAEmu to mice, following inoculation with BL cells, hinders tumor growth without toxic effects. To investigate the potential use of PNAEmu in clinical applications further, we tested its antigenicity. Mice were inoculated with an emulsion of free PNA or PNA crosslinked to the immunogenic carrier keyhole limpet hemocyanin (KLH) with Freund's adjuvant. Antibodies to free PNA were undetected, whereas both IgG and IgM antibodies to PNA-KLH were detected in mouse serum 28 and 38 days after inoculation.
Cutrona
Giovanna
G
SC. Oncologia Medica C, Istituto Nazionale per la Ricerca sul Cancro, IST, Genova, Italy. giovanna.cutrona@istge.it
Boffa
Lidia C
LC
Mariani
Maria Rita
MR
Matis
Serena
S
Damonte
Gianluca
G
Millo
Enrico
E
Roncella
Silvio
S
Ferrarini
Manlio
M
D000818:Animals; D002051:Burkitt Lymphoma / Q000188:drug therapy; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005803:Genes, Immunoglobulin; D006801:Humans; D007136:Immunoglobulins / Q000097:blood* / Q000235:genetics; D051379:Mice; D020135:Peptide Nucleic Acids / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D014178:Translocation, Genetic
D007136:Immunoglobulins; C519481:PNAEmu-NLS; D020135:Peptide Nucleic Acids; D016271:Proto-Oncogene Proteins c-myc