Application of nanotechnology in CAR-T-cell immunotherapy

Aim and Background: Chimeric antigen receptor (CAR) therapy has achieved exceptional clinical efficacy against hematological cancers and has been approved by FDA for treatment of B-cell tumors. However, in the field of solid tumors, the effectiveness of this therapy is hampered due to poor infiltration of CAR-T cells into solid tumor cells caused by the tumor microenvironment (TME), the inadequate trafficking of CAR-T cells as well as substantial antigen heterogeneity in solid tumors. Nanotechnology-based approaches can be exploited to overcome the challenges faced by T-cell therapies owing to the employment of nano-scale particles which possess interchangeable physicochemical properties. Methods: Herein, we review recent advances regarding the application of nanotechnology to improve CAR-T cell therapy by searching on “Google Scholar” database for publications. Results and discussion: The present face of nano interventions in CAR-T cell therapy has focused on improving various aspects of it; namely, (1) improving T cell manufacturing and transfecting tumor-specific CARs in T cells by utilizing nanoparticulate RNA vaccines, (2) overcoming T cell immunosuppression in the TME by using nanoparticles for photothermal therapy and cytokine delivery, (3) reducing systemic toxicity through introducing novel nanoformulations, (4) enhancing T cell tumor infiltration and prolonged persistence by inducing memory cell production, antigen spread or implementing nanocarriers with strong oxygen storage capacity. Conclusion: Given the unique attributes of nanomaterials to deliver, enhance, and regulate cancer immunotherapeutic agents, the combination of cancer immunotherapy with nanotechnology can radically change the landscape of cancer treatment.