Abstract
Immunotherapy has become a promising cancer therapy, improving the prognosis of patients with many different types of cancer and offering the possibility for long-term cancer remission. Nevertheless, some patients do not respond to these treatments and immunotherapy has shown some limitations, such as immune system resistance or limited bioavailability of the drug. Therefore, new strategies that include the use of nanoparticles (NPs) are emerging to enhance the efficacy of immunotherapies. NPs present very different pharmacokinetic and pharmacodynamic properties compared with free drugs and enable the use of lower doses of immune-stimulating molecules, minimizing their side effects. However, NPs face issues concerning stability in physiological conditions, protein corona (PC) formation, and accumulation in the target tissue. PC formation changes the physicochemical and biological properties of the NPs and in consequence their therapeutic effect. This review summarizes the recent advances in the study of the effects of PC formation in NP-based immunotherapy. PC formation has complex effects on immunotherapy since it can diminish (“immune blinding”) or enhance the immune response in an uncontrolled manner (“immune reactivity”). Here, future perspectives of the field including the latest advances towards the use of personalized protein corona in cancer immunotherapy are also discussed.
Highlights
Immunotherapy has attracted special attention in recent years as a novel cancer therapy, achieving durable and long-term responses in patients through the use of monoclonal antibodies or adoptive cell therapy [1,2]
This review summarizes the recent advances in the study of the effects of protein corona (PC) formation in NP-based immunotherapy
Rodell et al described the polarization of tumor-associated macrophages (TAMs) from M2 to M1 in multiple tumor models in mice [55].Using a monotherapy based on an agonist of the toll-like receptors (TLRs)loaded in β-cyclodextrin nanoparticles they altered the functional orientation of the tumor immune microenvironment towards an M1 phenotype, leading to a controlled tumor growth and the protection of the animals against tumor re-challenge
Summary
Immunotherapy has attracted special attention in recent years as a novel cancer therapy, achieving durable and long-term responses in patients through the use of monoclonal antibodies or adoptive cell therapy [1,2]. Rodell et al described the polarization of TAMs from M2 to M1 in multiple tumor models in mice [55].Using a monotherapy based on an agonist of the toll-like receptors (TLRs)loaded in β-cyclodextrin nanoparticles they altered the functional orientation of the tumor immune microenvironment towards an M1 phenotype, leading to a controlled tumor growth and the protection of the animals against tumor re-challenge Using this nano-formulation in combination with the immune checkpoint inhibitor anti-PD-1, they observed improved immunotherapy response rates in a tumor model resistant to anti-PD-1 therapy [55]. This is the mechanism by which cancer tissues limit the host immune response via up-regulation of the abovementioned PD-L1 and its binding to the programmed death-1 (PD-1) receptor on antigen-specific CD8+ T cells (termed adaptive immune resistance) [56,57] Therapies targeting these inhibitory receptors, for example PD-1 receptor, have shown outstanding rates of durable clinical responses in patients with different cancer types [58]. The modification of the surface of the particles is patient-specific and the formation of a PC may have additional undesired effects on the performance of the NPs including loss of efficacy of targeting moieties, undesired flagging by the complement, unspecific uptake by immune cells, and immunotoxicity
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