Advanced Nanotechnology for Enhancing Immune Checkpoint Blockade Therapy

Abstract

Immune checkpoint receptor signaling pathways constitute a prominent class of “immune synapse,” a cell-to-cell connection that represses T-lymphocyte effector functions. As a possible evolutionary countermeasure against autoimmunity, this strategy is aimed at lowering potential injury to uninfected cells in infected tissues and at minimizing systemic inflammation. Nevertheless, tumors can make use of these strategies to escape immune recognition, and consequently, such mechanisms represent chances for immunotherapy intervention. Recent years have witnessed the advance of pharmaceutical nanotechnology, or nanomedicine, as a possible strategy to ameliorate immunotherapy technical weaknesses thanks to its intrinsic biophysical properties and multifunctional modifying capability. To improve the long-lasting response rate of checkpoint blockade therapy, nanotechnology has been employed at first for the delivery of single checkpoint inhibitors. Further, while therapy via single immune checkpoint blockade determines resistance and a restricted period of response, strong interest has been raised to efficiently deliver immunomodulators targeting different inhibitory pathways or both inhibitory and costimulatory pathways. In this review, the partially explored promise in implementation of nanotechnology to improve the success of immune checkpoint therapy and solve the limitations of single immune checkpoint inhibitors is debated. We first present the fundamental elements of the immune checkpoint pathways and then outline recent promising results of immune checkpoint blockade therapy in combination with nanotechnology delivery systems.

Application Perspectives of Nanomedicine in Cancer Treatment

“…Based on the above, the role of nanomaterials in immunotherapy has gone beyond the concept of adjuvant or carrier, which is an effective means to improve the efficacy of ICIs and reduce their toxicity through rational design. At the same time, the dosing cycle and interval time, possible off-target potential and other aspects should be improved to obtain the best solution ( Cremolini et al, 2021 ).…”

Nanomedicine approaches for treatment of hematologic and oncologic malignancies

“…The role of nanomedicine in ICIs is to ensure an increased therapeutic outcome by using specific nanocarriers. Several formulations are currently investigated in both pre-clinical and clinical studies[ 42 ]. Starting from the preclinical studies, at least 12 different nanocarriers are being investigated.…”

“…These mainly include Nanoparticle Albumin Bound (Nab) formulations that combine ICIs with standard chemotherapeutics (as in the case of paclitaxel and carboplatin in Pembrolizumab, Atezolizumab, and Nivolumab formulations). Non-Nab strategies in nanoparticle-based immunotherapy include the radiosensitizer molecule NBTXR3[ 42 ].…”

Lipid Nanoparticles for mRNA Delivery to Enhance Cancer Immunotherapy

“…It artificially activates the immune system by regulating and controlling the working mechanisms of the immune system, rather than targeting the tumor itself, in order to clear malignant tumor cells. Available therapies are cancer vaccines [ 3 , 4 , 5 ], adoptive cell therapy (ACT) [ 6 , 7 , 8 , 9 ], immune checkpoint blockade (ICB) [ 10 , 11 , 12 , 13 , 14 ], and cytokines [ 15 ]. Cancer immunotherapy is well established and current immune agents include vaccines, T cell activators, dendritic cell (DC) stimulators, and immune checkpoint inhibitors [ 16 ], whose therapeutic principle is mainly T cell-regulated antitumor immunity, but the effector function of T cells is not autonomous, and effective immune responses may be negatively regulated by tumor regulatory T cells (Tregs) influence [ 17 , 18 ].…”