Abstract
Nanomedicines have shown great potential in cancer therapy; in particular, the combination of chemotherapy and immunotherapy (namely chemoimmunotherapy) that is revolutionizing cancer treatment. Currently, most nanomedicines for chemoimmunotherapy are still in preclinical and clinical trials. Lipid-based nanoparticles, the most widely used nanomedicine platform in cancer therapy, is a promising delivery platform for chemoimmunotherapy. In this review, we introduce the commonly used immunotherapy agents and discuss the opportunities for chemoimmunotherapy mediated by lipid-based nanoparticles. We summarize the clinical trials involving lipid-based nanoparticles for chemoimmunotherapy. We also highlight different chemoimmunotherapy strategies based on lipid-based nanoparticles such as liposomes, nanodiscs, and lipid-based hybrid nanoparticles in preclinical research. Finally, we discuss the challenges that have hindered the clinical translation of lipid-based nanoparticles for chemoimmunotherapy, and their future perspectives.
Highlights
Cancer chemoimmunotherapy is a treatment that utilizes the synergistic benefits of chemotherapy and immunotherapy
Food and Drug Administration (FDA) in 1986 for hairy cell leukemia, early-stage cancer immunotherapy from cytokines to interleukin-2 (IL-2) has shown limited therapeutic effect with high toxicity [1,2]. This situation was greatly improved when the pioneering checkpoint inhibitor ipilimumab, a monoclonal antibody that targets Cytotoxic T-lymphocyteassociated protein 4 (CTLA4), was approved for the treatment of advanced melanoma in 2011 by the FDA, which was featured by Science as the breakthrough of the year in 2013 [3,4]
Cancer immunotherapy has been shown to be effective in treating certain cancers and has been approved by the FDA to treat melanoma, non-small
Summary
Chemotherapy has served as the standard-of-care cancer treatment for a long time. It has been shown that the combination of chemotherapy and immunotherapy is a potential strategy in cancer therapy due to the synergistic effects on the TME. The repolarization of tumor-promoting M2-type tumor-associated macrophages (TAMs) into the tumor-suppressing M1 type has been observed in mice upon administration of PTX [71] Combination of these chemotherapeutic agents with other immune activators seems to provide enhanced antitumor immune response in the TME. In addition to the effects on cancer and immune cells directly, some conventional chemotherapeutic agents may cause some “off-target” side effects on the whole-body immune response involving multiple pathways, such as gastrointestinal toxicity affecting the gut microbiota and upregulation of systemic immunosuppressive factors [72,73]. The combination of these chemotherapeutic agents with immune modulators, which reverses the immunosuppressive microenvironment and improves chemotherapeutic effect, is regarded as a complementary mechanism to enhance antitumor effect. Combination of chemotherapeutic agents with immunotherapy can augment antitumor response in the TME, improving cancer treatment
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