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Title (Primary) A minigene DNA vaccine encoding peptide epitopes derived from Galectin-1 has protective antitumoral effects in a model of neuroblastoma
Author Liebscher, L.; Weißenborn, C.; Langwisch, S.; Gohlke, B.-O.; Preissner, R.; Rabinovich, G.A.; Christiansen, N.; Christiansen, H.; Zenclussen, A.C.; Fest, S.;
Journal Cancer Letters
Year 2021
Department IMMU;
Volume 509
Language englisch;
Keywords Galectin-1; Neuroblastoma; DNA vaccine; Salmonella typhimurium; Immunotherapy
Abstract

We recently identified Galectin-1 (Gal-1), a β-galactoside-binding lectin, as a novel immune regulator in neuroblastoma (NB). Here, we characterized the tolerogenic function of Gal-1 within the CD8+ T cell compartment and further evaluated its relevance as an antigen for effective DNA vaccination against NB in a mouse model. NB cells with Gal-1 knockdown (NXS-2L) exhibited significantly reduced tumor growth compared to NXS-2 NB cells. Administration of anti-CD8 antibodies prevented this antitumor effect, with primary tumor growth comparable to that from Gal-1 (G1)-sufficient NB cells. Peptide epitope screening with online databases and in silico docking experiments predicted the sequences “FDQADLTI” (#1), “GDFKIKCV” (#2), and “AHGDANTI” (#3) to have superior H2-KK binding affinities and “KFPNRLNM” (#4), “DGDFKIKCV” (#5), and “LGKDSNNL” (#6) to have superior H2-DD binding affinities. Minigenes encoding G1-KK (#1-#2-#3), G1-DD (#4-#5-#6) and the triplet with the highest affinity, G1-H (#1-#2-#4), were generated and cloned into a ubiquitin-containing plasmid (pU). Mice receiving pU-G1-KK or pU-G-1H presented a reduction in the s.c. tumor volume and weight of up to 80% compared to control mice; this reduction was associated with increased cytotoxicity of isolated splenocytes from vaccinated animals. Vaccination with pUG1-DD showed a lower capability to suppress primary tumor progression. In conclusion, Gal-1 expression by NB negatively regulates CD8+ T cells. Vaccination with DNA plasmids encoding Gal-1 epitopes overcomes immune escape, enhances CD8+ T cell-dependent immunity and displays effective antitumor activity against NB.

ID 24513
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=24513
Liebscher, L., Weißenborn, C., Langwisch, S., Gohlke, B.-O., Preissner, R., Rabinovich, G.A., Christiansen, N., Christiansen, H., Zenclussen, A.C., Fest, S. (2021):
A minigene DNA vaccine encoding peptide epitopes derived from Galectin-1 has protective antitumoral effects in a model of neuroblastoma
Cancer Lett. 509 , 105 - 114