Immune response recalibration using immune therapy and biomimetic nano-therapy against high-grade gliomas and brain...

Although with aggressive standards of care like surgical resection, chemotherapy, and radiation, high-grade gliomas (HGGs) and brain metastases (BM) treatment has remained challenging for more than two decades. However, technological advances in this field and immunotherapeutic strategies have revolutionized the treatment of HGGs and BM. Immunotherapies like immune checkpoint inhibitors, CAR-T targeting, oncolytic virus-based therapy, bispecific antibody treatment, and vaccination approaches, etc., are emerging as promising avenues offering new hope in refining patient's survival benefits. However, selective trafficking across the blood-brain barrier (BBB), immunosuppressive tumor microenvironment (TME), metabolic alteration, and tumor heterogeneity limit the therapeutic efficacy of immunotherapy for HGGs and BM. Furthermore, to address this concern, the NanoBioTechnology-based bioinspired delivery system has been gaining tremendous attention in recent years. With technological advances such as Trojan horse targeting and infusing/camouflaging nanoparticles surface with biological molecules/cells like immunocytes, erythrocytes, platelets, glioma cell lysate and/or integrating these strategies to get hybrid membrane for homotypic recognition. These biomimetic nanotherapy offers advantages over conventional nanoparticles, focusing on greater target specificity, increased circulation stability, higher active loading capacity, BBB permeability (inherent inflammatory chemotaxis of neutrophils), decreased immunogenicity, efficient metabolism-based combinatorial effects, and prevention of tumor recurrence by induction of immunological memory, etc. provide new age of improved immunotherapies outcomes against HGGs and BM. In this review, we emphasize on neuro-immunotherapy and the versatility of these biomimetic nano-delivery strategies for precise targeting of hard-to-treat and most lethal HGGs and BM. Moreover, the challenges impeding the clinical translatability of these approaches were addressed to unmet medical needs of brain cancers.