Targeting Vesicular LGALS3BP by an Antibody-Drug Conjugate as Novel Therapeutic Strategy for Neuroblastoma

Emily Capone, Alessia Lamolinara, Fabio Pastorino, Roberta Gentile, Sara Ponziani, Giulia Di Vittorio, Daniela D'Agostino, Sandra Bibbò, Cosmo Rossi, Enza Piccolo, Valentina Iacobelli, Rossano Lattanzio, Valeria Panella, Michele Sallese, Vincenzo De Laurenzi, Francesco Giansanti, Arturo Sala, Manuela Iezzi, Mirco Ponzoni, Rodolfo IppolitiStefano Iacobelli, Gianluca Sala

Research output: Contribution to journalArticlepeer-review

Abstract

Neuroblastoma is the most common extra-cranial solid tumor in infants and children, which accounts for approximately 15% of all cancer-related deaths in the pediatric population. New therapeutic modalities are urgently needed. Antibody-Drug Conjugates (ADC)s-based therapy has been proposed as potential strategy to treat this pediatric malignancy. LGALS3BP is a highly glycosylated protein involved in tumor growth and progression. Studies have shown that LGALS3BP is enriched in extracellular vesicles (EV)s derived by most neuroblastoma cells, where it plays a critical role in preparing a favorable tumor microenvironment (TME) through direct cross talk between cancer and stroma cells. Here, we describe the development of a non-internalizing LGALS3BP ADC, named 1959-sss/DM3, which selectively targets LGALS3BP expressing neuroblastoma. 1959-sss/DM3 mediated potent therapeutic activity in different types of neuroblastoma models. Notably, we found that treatments were well tolerated at efficacious doses that were fully curative. These results offer preclinical proof-of-concept for an ADC targeting exosomal LGALS3BP approach for neuroblastomas.

Original languageEnglish
JournalCancers
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 15 2020

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