Advances in Nanotechnology Development to Overcome Current Roadblocks in CAR-T Therapy for Solid Tumors

Abstract

Chimeric antigen receptor T cell (CAR-T) therapy for the treatment of hematologic tumors has achieved remarkable success, with five CAR-T therapies approved by the United States Food and Drug Administration. However, the efficacy of CAR-T therapy against solid tumors is not satisfactory. There are three existing hurdles in CAR-T cells for solid tumors. First, the lack of a universal CAR to recognize antigens at the site of solid tumors and the compact tumor structure make it difficult for CAR-T cells to locate in solid tumors. Second, soluble inhibitors and suppressive immune cells in the tumor microenvironment can inhibit or even inactivate T cells. Third, low survival and proliferation rates of CAR-T cells in vivo significantly influence the therapeutic effect. As an emerging method, nanotechnology has a great potential to enhance cell proliferation, activate T cells, and restarting the immune response. In this review, we discuss how nanotechnology can modify CAR-T cells through variable methods to improve the therapeutic effect of solid tumors.

Harnessing immunotherapy for brain metastases: insights into tumor–brain microenvironment interactions and emerging treatment modalities

“…CAR-T cells will also benefit from the construction of nanodelivery systems: (i) the formulation of unique spaces, such as hydrogels, for the storage, release and potential activation assistance of CAR-T cells; (ii) the delivery of ICIs to bolster CAR-T cells, or even direct CAR mRNA delivery to prompt native T cells; and (iii) the use of physical response properties, such as light, heat, sound or magnetism, to assist CAR-T cells in better navigating and functioning within the TME [ 114 , 190 , 204 , 207 ].…”

“…Alternatively, nanomaterials can be directly used to conceive micro scaffolds with T cell growth promoting factors, hence establishing a microenvironment for in vivo amplification of CAR-T cells. Furthermore, nanogel or mRNA nanocarrier delivery systems will also provide a novel research mentality [ 114 , 189 , 190 , 204 ].…”

Advances in nano-immunotherapy for hematological malignancies

“…For instance, the combination of microwave ablation and AXL-CAR T cells has demonstrated superior anti-tumor efficacy in AXL-positive non-small cell lung cancer patient-derived xenograft tumors, achieved through TME remodeling [ 157 ]. Recently, nanotechnology has been employed to remodel the immunosuppressive TME, promoting the activation of CAR-T cells [ 158 ]. Nanozymes with natural enzyme-like activities have been extensively studied as a means to regulate TME by initiating intratumoral nanocatalytic chemical reactions.…”

Emerging role of nanotechnology in cancer immunotherapy

“…Therefore, targeting TAMs or TME to evoke cancer cell killing through cellular phagocytosis have become a promising malignancy immunotherapy. Combining nanotechnology with this strategy has become an emerging trend to get rid of the drawbacks of this strategy, such as the lack of efficiency [20]. Zhao C et al summarized different therapeutic pathways based on nanotechnology to modulate macrophage's function [21]:…”