A minigene DNA vaccine encoding peptide epitopes derived from Galectin-1 has protective antitumoral effects in a model of neuroblastoma

LAURA LIEBSCHER; CHRISTINE WEISENBORN; STEFANIE LANGWISCH; BJÖRN-OLIVER GOHLKE; ROBERT PREISSNER; GABRIEL RABINOVICH; NINA CHRISTIANSEN; HOLGER CHRISTIANSEN; ANA ZENCLUSSEN; STEFAN FEST

CANCER LETTERS

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2021 vol. 1 p. 105 - 114

0304-3835

We recently identified Galectin-1 (Gal-1), a -galactoside-binding lectin, as a novel immuneregulator in neuroblastoma (NB). Here, we characterized the function of Gal-1 on CD8 T cellfunction and further evaluated role of Gal-1 as promising antigen for effective DNA vaccinationagainst NB.When Gal-1 was knock-downed in NB cells (NXS-2L), tumor growth was significantly reducedcompared to NXS-2 NB cells. Anti-CD8 injections reversed this situation, with primary tumorcomparable to Gal-1 (G1) competent NB cells. Peptide epitope screening with online databasesand computer docking experiments predicted the sequences ?FDQADLTI? (#1), ?GDFKIKCV?(#2), ?AHGDANTI? (#3) to have superior H2-KK and ?KFPNRLNM? (#4), ?DGDFKIKCV?(#5), ?LGKDSNNL? (#6) to have superior H2-DD binding affinities. Minigenes encoding forG1-KK (#1-#2-#3), G1-DD (#4-#5-#6) or a triplet of highest affinity G1-H (#1-#2-#4) weregenerated and cloned into a ubiquitin containing plasmid (pU). Mice receiving the pUG1-KK orpUG-1H presented up to 80% reduction in s.c. tumor volume and weight compared to controls;this was associated with increased cytotoxicity of isolated splenocytes. Vaccination with pUG1-DD showed less suppressive capabilities on primary tumor progression.In conclusion Gal-1 expression by NB negatively regulates CD8+ T cells. Vaccination with Gal-1-encoding DNA plasmids overcomes immune escape and is effective against NB.