Jun Wei et al. developed the 4-1-BB–Osteopontin (OPN) bispecific aptamer, composed of the OPN-R3 aptamer, against osteopontin (OPN; a glycophosphoprotein upregulated in GBM-infiltrating immune cells such as macrophages and associated with poor survival in GBM patients), to block M0 and M2 macrophage migration, and the A4-1BB aptamer, to promote the survival and expansion of CD8+ T cells. Here, SPP1 is linked to glioblastoma.