Targeted attack: Harnessing myelin-specific plasmolipin for suppression of neuroblastoma and glioblastoma

There is a growing urgency to develop effective strategies for studying and targeting glioblastoma including, which are crucial for tumor initiation and resistance to therapy. Human-immunodeficiency-virus-type-1-based viral particles have emerged as valuable tools in neurology, aiding in the exploration of neural development and tumorigenesis, with promising clinical applications on the horizon. We targeted proteolipid plasmolipin, found on glial cell surfaces, acting as an entry receptor for the McERV endogenous murine retrovirus, with replication-defective vectors carrying either a fluorescent marker or the suicide gene TK.007, pseudotyped with the McERV envelope protein. We evaluated these vectors' efficiency in delivering genes to glioblastoma and neuronal cells both <i>in vitro</i> and <i>in vivo</i>, using intracranial glioblastoma and subcutaneous neuroblastoma xenograft tumors. Our findings confirm that aiming plasmolipin allows efficient and selective elimination of tumors induced by plasmolipin-positive cancer cells while sparing normal tissue. This work highlights the potential of McERV-pseudotyped viral particles as a promising therapeutic strategy for targeting glioblastoma and neuronal tumors.