Background
Antibody Drug Conjugates (ADC)s are an emerging class of biopharmaceuticals that have seen an impressive
increase of attention in the field of cancer therapy. Recent studies have proved that ADC with non-internalizing
antibody can be used to efficiently target tumor or stroma cells also. We have developed a new type of noninternalizing
ADC, named 1959sss/DM3, targeting Gal-3BP, a secreted protein largely expressed by the
majority of human tumors, while being virtually undetectable in normal adult tissues. Our preliminary data
strongly support the hypothesis that Gal-3BP may be an excellent therapeutic target in neuroblastoma and
glioblastoma. Importantly we confirmed that the ADC accumulates in Gal-3BP positive but not in negative
tumor tissue, promoting tumor shrinkage in a target-dependent fashion. We hypothesize that the ADC might
work by recognizing the antigen expressed both on the tumor cell surface and the extracellular matrix,
releasing the drug in the reducing space of tumor micro-environment, resulting in a potent therapeutic effect.
Hypothesis
Gal-3BP is a secreted protein enriched in cancer-derived extracellular vesicles (EV)s. Our preliminary data
strongly indicates that Gal-3BP may represent an ideal target for non-internalizing ADC therapy. We believe
that, if successful, our study will pave the way to a more effective therapeutic approach for neuroblastoma and
glioblastoma.
Aims
- Assessment of the role of Gal-3BP in the regulation of tumor microenvironment and immune system;
- Defining ADC mechanism/s of action;
- Preclinical evaluation of anti-Gal-3BP ADC therapeutic activity in neuroblastoma and glioblastoma;