Abstract

Current cancer immunotherapy has limited response rates in a large variety of solid tumors partly due to the low immunogenicity of the tumor cells and the immunosuppressive tumor microenvironment (ITM). A number of clinical cancer treatment modalities, including radiotherapy, chemotherapy, photothermal and photodynamic therapy, have been shown to elicit immunogenicity by inducing immunogenic cell death (ICD). However, ICD-based immunotherapy is restricted by the ITM limiting its efficacy in eliciting a long-term antitumor immune response, and by severe systemic toxicity. To address these challenges, nanomedicine-based drug delivery strategies have been exploited for improving cancer immunotherapy by boosting ICD of the tumor cells. Nanosized drug delivery systems are promising for increasing drug accumulation at the tumor site and codelivering ICD inducers and immune inhibitors to simultaneously elicit the immune response and relieve the ITM. This review highlights the recent advances in nanomedicine-based immunotherapy utilizing ICD-based approaches. A perspective on the clinical translation of nanomedicine-based cancer immunotherapy is also provided.

Highlights

  • 1234567890();,: INTRODUCTION Cancer immunotherapy has changed the paradigm of clinical cancer therapy by demonstrating that boosting the systemic immune response can lead to tumor regression [1, 2]

  • Despite the potential of immunotherapy to cure malignant tumors, the clinical application of current cancer immunotherapy has been hampered by several challenges, including insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the immunosuppressive tumor microenvironment (ITM) [3, 4]

  • To improve the therapeutic performance of Immunogenic cell death (ICD)-based cancer immunotherapy, nanoparticle-based drug delivery systems enable codelivery and multiple irradiation regimens to enhance the performance of ICD-based therapies

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Summary

Introduction

Cancer immunotherapy has changed the paradigm of clinical cancer therapy by demonstrating that boosting the systemic immune response can lead to tumor regression [1, 2]. Nanoparticles enable targeted drug accumulation at the tumor site, enhance tissue penetration and increase cellular uptake, as well as trigger the tailored release of ICD inducers [35–40]. CpG-loaded lipidpolymer hybrid nanoparticles containing mitoxantrone induced an antigen-specific CD8+ T cell response with a higher level of ICD than did mitoxantrone administered alone and significantly inhibited tumor growth in a CT26 tumor model [49].

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