A Bi-Specific T Cell-Engaging Antibody Shows Potent Activity, Specificity, and Tumor Microenvironment Remodeling in Experimental Syngeneic and Genetically Engineered Models of GBM.

Background: Bispecific T cell-engagers (BTEs) are engineered antibodies that redirect T cells to target antigen-expressing tumors. BTEs targeting various tumor-specific antigens, like interleukin 13 receptor alpha 2 (IL13RA2) and EGFRvIII, have been developed for glioblastoma (GBM). However, limited knowledge of BTE actions derived from studies conducted in immunocompromised animal models impedes progress in the field.

IL15 modification enables CAR T cells to act as a dual targeting agent against tumor cells and myeloid-derived suppressor cells in GBM.

Introduction: The immunosuppressive tumor microenvironment (TME) is a major barrier to the efficacy of chimeric antigen receptor T cells (CAR-T cells) in glioblastoma (GBM). Transgenic expression of IL15 is one attractive strategy to modulate the TME. However, at present, it is unclear if IL15 could be used to directly target myeloid-derived suppressor cells (MDSCs), a major cellular component of the GBM TME.

Indocarbocyanine nanoparticles extravasate and distribute better than liposomes in brain tumors.

Glioblastoma (GBM) is the most devastating and aggressive brain tumor in adults. Hidden behind the blood-brain and blood-tumor barriers (BBTB), this invasive type of brain tumor is not readily accessible to nano-sized particles. Here we demonstrate that fluorescent indocarbocyanine lipids (ICLs: DiD, DiI) formulated in PEGylated lipid nanoparticle (PLN) exhibit highly efficient penetration and accumulation in GBM.