A Cisplatin‐Loaded Immunochemotherapeutic Nanohybrid Bearing Immune Checkpoint Inhibitors for Enhanced Cervical Cancer Therapy

Wang, Na; Wang, Zhigang; Xu, Zoufeng; Chen, Xianfeng; Zhu, Guangyu

doi:10.1002/anie.201800422

Cited by 102 publications

(50 citation statements)

References 54 publications

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“…Chemotherapies have the advantages of fast-acting and high response rate and are widely administrated as the primary treatment for combinational strategies 34 . Combinations of chemotherapies with immunotherapies are widely discussed and currently tested in pre-clinical models and clinical trials 17,[35][36][37] . Mechanistically, chemotherapy can promote anti-tumor immunity via inducing immunogenic cell death and disrupting tumor microenvironment components that are used to evade the immune response [38][39][40][41][42] .…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy but not the tumor draining lymph nodes determine the immunotherapy response in secondary tumors

Zhao

Kassaye

Wangmo

et al. 2019

Preprint

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SUMMARYImmunotherapies are used as adjuvant therapies for cancers. However, knowledge of how traditional cancer treatments affect immunotherapies is limited. Using mouse models, we demonstrate that tumor-draining lymph nodes (TdLNs) are critical for tumor antigen-specific T-cell response. However, removing TdLNs concurrently with established primary tumors did not affect the immune checkpoint blockade (ICB) response on localized secondary tumor due to immunotolerance in TdLNs and distribution of antigen-specific T cells in peripheral lymphatic organs. Notably, treatment response improved with sequential administration of 5-fluorouracil (5-FU) and ICB compared to concurrent administration of ICB with 5-FU. Immune profiling revealed that using 5-FU as induction treatment increased tumor visibility to immune cells, decreased immunosuppressive cells in the tumor microenvironment, and limited chemotherapy-induced T-cell depletion. We show that the effect of traditional cytotoxic treatment, not TdLNs, influences immunotherapy response in localized secondary tumors. We postulate essential considerations for successful immunotherapy strategies in clinical conditions.Graphic abstractThe effects of tumor-draining lymph nodes (TdLNs) resection and a combination of cytotoxic chemotherapy on immune checkpoint blockade therapies are evaluated in this study. TdLNs resection was adverse in eliciting an antitumor immune response in early-stage tumors, but not in late-stage tumors. Further, sequential treatments with cytotoxic chemotherapy and immunotherapy showed better tumor control compared to concurrent combinatorial treatments.

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Section: Discussionmentioning

confidence: 99%

Chemotherapy but not the tumor draining lymph nodes determine the immunotherapy response in secondary tumors

Zhao

Kassaye

Wangmo

et al. 2019

Preprint

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“…These immunosuppressive effects can be revived by IDO inhibitors, and the efficacy can be further enhanced through a nano‐enabled approach. An example is layered double hydroxide (LDH) nanoparticles coloaded with IDO inhibitor and cisplatin prodrug ( Figure ) . These multifunctional nanocarriers not only boosted the apoptosis of cervical cancer cells compared with free cisplatin but also dramatically decreased the production of Kyn to simultaneously potentiate effector T cell differentiation in the tumor microenvironment.…”

Section: Delivery System For Provoking Antitumor Immunitymentioning

confidence: 99%

Section: Delivery System For Provoking Antitumor Immunitymentioning

confidence: 99%

“…Small 2019, 15,1900262 FA-modified PEI 170 Anti-PD-L1 [144] Disulfide-cross-linked PEI 200-300 siPD-L1 [145] Alginate hydrogel Anti-PD-1 + celecoxib [146] Immune-tolerant elastin-like polypeptide 45 Anti-PD-1 [147] PLGA nanoparticles 180 Anti-CTLA-4 [148] Maleimide-terminated PEG-PLGA nanoparticles 160 Anti-PD-L1 + anti-OX-40 [149] Lipid-based Lipid calcium phosphate nanoparticles 45 pPD-L1 + pCXCL12 [150] Cationic lipid SAINT-18 siPD-L1 + siPD-L2 [151] Liposomal cerasome nanoparticles 90-150 Anti-PD-L1 + paclitaxel [152] Inorganic Iron oxide nanoparticles 80 Anti-PD-L1 + anti-4-lBB [153] Mesoporous silica nanoparticles 30 Anti-CTLA-4 [154] Fucoidan-based iron oxide nanoparticles 142 Anti-PD-L1 + anti-CD3/anti-CD28 [155] Cell-based Platelets 100-200 Anti-PD-L1 [156] siRNA with mitochondrion-targeting photosensitizer for photodynamic therapy (PDT) in one tumor pH-sensitive micellar nanocomplex, consisting of a PEG shielding layer, a PEI middle layer, and a poly(2-(diethylamino) ethyl methacrylate (PDEA) core (Figure 6). [159] The PEG layer helps prolong the circulation time and is shed in response to the weak acidity in the tumor microenvironment.…”

Section: Et Al Integrated Pd-l1-blockablementioning

confidence: 99%

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Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Liu

Zhang

2019

Small

116

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Cancer immunotherapy is a promising cancer terminator by directing the patient's own immune system in the fight against this challenging disorder. Despite the monumental therapeutic potential of several immunotherapy strategies in clinical applications, the efficacious responses of a wide range of immunotherapeutic agents are limited in virtue of their inadequate accumulation in the tumor tissue and fatal side effects. In the last decades, increasing evidences disclose that nanotechnology acts as an appealing solution to address these technical barriers via conferring rational physicochemical properties to nanomaterials. In this Review, an imperative emphasis will be drawn from the current understanding of the effect of a nanosystem's structure characteristics (e.g., size, shape, surface charge, elasticity) and its chemical modification on its transport and biodistribution behavior. Subsequently, rapid‐moving advances of nanoparticle‐based cancer immunotherapies are summarized from traditional vaccine strategies to recent novel approaches, including delivery of immunotherapeutics (such as whole cancer cell vaccines, immune checkpoint blockade, and immunogenic cell death) and engineered immune cells, to regulate tumor microenvironment and activate cellular immunity. The future prospects may involve in the rational combination of a few immunotherapies for more efficient cancer inhibition and elimination.

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“…The lack of tryptophan in the tumoral tissue leads to T cell anergy. Wang et al have synthesized layered double oxide nanoparticles (LDH) loaded with a potent IDO inhibitor (4-{[2-(4-bromophenyl)hydrazinyl]sulfonyl}benzoic acid) and the prodrug disuccinatocisplatin [72]. Once the nanocarriers were engulfed by tumoral cells, Pt(IV) of the prodrug was converted into highly toxic Pt(II) by the reductive cytosolic environment inducing tumoral cell apoptosis, whereas the released IDO inhibitor blocked the action of the enzyme that allowed the action of infiltrated cytotoxic T cells.…”

Section: Nanoparticles To Enhance the Antitumoral Action Of Adaptive mentioning

confidence: 99%

Tumor Targeted Nanocarriers for Immunotherapy

Baeza

2020

Molecules

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The paramount discovery of passive accumulation of nanoparticles in tumoral tissues triggered the development of a wide number of different nanoparticles capable of transporting therapeutic agents to tumoral tissues in a controlled and selective way. These nanocarriers have been endowed with important capacities such as stimuli-responsive properties, targeting abilities, or the capacity to be monitored by imaging techniques. However, after decades of intense research efforts, only a few nanomedicines have reached the market. The reasons for this disappointing outcome are varied, from the high tumor-type dependence of enhanced permeation and retention (EPR) effect to the poor penetration capacity of nanocarriers within the cancerous tissue, among others. The rapid nanoparticle clearance by immune cells, considered another important barrier, which compromises the efficacy of nanomedicines, would become an important ally in the fight against cancer. In the last years, the fine-tuned ability of immune cells to recognize and engulf nanoparticles have been exploited to deliver immunoregulating agents to specific immune cell populations selectively. In this work, the recent advances carried out in the development of nanocarriers capable of operating with immune and tumoral cells in order to orchestrate an efficient antitumoral response will be presented. The combination of nanoparticles and immunotherapy would deliver powerful weapons to the clinicians that offer safer and more efficient antitumoral treatments for the patients.

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A Cisplatin‐Loaded Immunochemotherapeutic Nanohybrid Bearing Immune Checkpoint Inhibitors for Enhanced Cervical Cancer Therapy

Cited by 102 publications

References 54 publications

Chemotherapy but not the tumor draining lymph nodes determine the immunotherapy response in secondary tumors

Chemotherapy but not the tumor draining lymph nodes determine the immunotherapy response in secondary tumors

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Tumor Targeted Nanocarriers for Immunotherapy

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