Targeting glycosaminoglycans in solid tumors

Glycosaminoglycans (GAGs) are post-translational secondary modifications to proteins and a major component of the tumor glycocalyx. GAGs shape tumor behavior in many ways and play important roles for proliferation, motility, and plasticity of solid tumors. Most solid tumors present with highly sulfated variants of chondroitin sulfate (CS) GAGs that are shared only with placental trophoblast cells, constituting a specific and broad oncofetal GAG targeting opportunity in solid tumor pediatric and adult cancer indications. We have developed an oncofetal CS-targeting technology based on an evolutionarily refined malaria protein called VAR2CSA that can be utilized for targeted delivery of anti-cancer cytotoxic payloads as well as immunotherapy applications. I will present previous and current efforts of targeting oncofetal CS in solid tumors and discuss opportunities and challenges for clinical translation.