Engineering nanoparticles to locally activate T cells in the tumor microenvironment

Wang, Dangge; Wang, Tingting; Yu, Haijun; Feng, Bing; Zhou, Lei; Zhou, Fangyuan; Hou, Bo; Zhang, Hanwu; Luo, Min; Li, Yaping

doi:10.1126/sciimmunol.aau6584

Cited by 213 publications

(161 citation statements)

References 62 publications

Supporting

Mentioning

158

Contrasting

Unclassified

Order By: Relevance

“…As shown in Figure A, the T1 signal in the subcutaneous tumor site increased significantly at 12 h after intravenous injection of micelle and then maintained at high level up to 24 h, demonstrating that the nanodrug could be effectively delivered to the melanoma site. Notably, compared with AMcP, the sAMcP accumulated more efficiently in the tumor site at 24 h after injection (Figure 5B), which could be attributed to the reduced macrophage phagocytosis and prolonged circulation time of nanodrug caused by the long chain PEG shielding strategy . Distribution of nanodrugs in the major organs was also determined by quantitatively analyzing the Mn concentration using inductively coupled plasma‐optical emission spectrometer (ICP‐OES).…”

Section: Resultsmentioning

confidence: 99%

Codelivery of Anti‐PD‐1 Antibody and Paclitaxel with Matrix Metalloproteinase and pH Dual‐Sensitive Micelles for Enhanced Tumor Chemoimmunotherapy

Xiao

Wang

et al. 2020

Small

View full text Add to dashboard Cite

Immune checkpoint blockade (ICB) is demonstrating great potential in cancer immunotherapy nowadays. Yet, the low response rate to ICB remains an urgent challenge for tumor immunotherapy. A pH and matrix metalloproteinase dual‐sensitive micellar nanocarrier showing spatio‐temporally controlled release of anti‐PD‐1 antibody (aPD‐1) and paclitaxel (PTX) in solid tumors is prepared to realize synergistic cancer chemoimmunotherapy. Antitumor immunity can be activated by PTX‐induced immunogenic cell death (ICD), while aPD‐1 blocks the PD‐1/PD‐L1 axis to suppress the immune escape due to PTX‐induced PD‐L1 up‐regulation, thus resulting in a synergistic antitumor chemoimmunotherapy. Through decoration with a sheddable polyethylene glycol (PEG) shell, the nanodrug may better accumulate in tumors to boost the synergistic antitumor treatment in a mouse melanoma model. The present study demonstrates a potent antitumor chemoimmunotherapy utilizing tumor microenvironment‐sensitive micelles bearing a sheddable PEG layer to mediate site‐specific sequential release of aPD‐1 and PTX.

show abstract

Section: Resultsmentioning

confidence: 99%

Codelivery of Anti‐PD‐1 Antibody and Paclitaxel with Matrix Metalloproteinase and pH Dual‐Sensitive Micelles for Enhanced Tumor Chemoimmunotherapy

Xiao

Wang

et al. 2020

Small

View full text Add to dashboard Cite

show abstract

“…[60][61][62] Briefly, PTX was dissolved in the mixed solvent of polyoxyethylated castor oil (Cremo phor EL) and anhydrous ethanol (1:1, v/v) and then added into saline solution to obtain PTX solution at a cremophor/ethanol/ saline volume ratio of 1/1/8. When the tumor volume reached 100 mm 3 , the tumor bearing mice was intravenously (i.v.)…”

Section: Biodistribution Of Ispn In Vivomentioning

confidence: 99%

Enhancing Triple Negative Breast Cancer Immunotherapy by ICG‐Templated Self‐Assembly of Paclitaxel Nanoparticles

Feng

Niu

Hou

et al. 2019

Adv Funct Materials

Self Cite

161

115

View full text Add to dashboard Cite

Combination cancer immunotherapy has shown promising potential for simultaneously eliciting antitumor immunity and modulating the immunosuppressive tumor microenvironment (ITM). However, combination immunotherapy with multiple regimens suffers from the varied chemophysical properties and inconsistent pharmacokinetic profiles of the different therapeutics. To achieve tumor-specific codelivery of the immune modulators, an indocyanine green (ICG)-templated self-assembly strategy for preparing dual drug-loaded two-in-one nanomedicine is reported. ICG-templated self-assembly of paclitaxel (PTX) nanoparticles (ISPN), and the application of ISPN for combination immunotherapy of the triple negative breast cancer (TNBC) are demonstrated. The ISPN show satisfied colloidal stability and high efficacy for tumor-specific codelivery of ICG and PTX through the enhanced tumor permeability and retention effect. Upon laser irradiation, the ICG component of ISPN highly efficiently induces immunogenic cell death of the tumor cells via activating antitumor immune response through photodynamic therapy. Meanwhile, PTX delivered by ISPN suppresses the regulatory T lymphocytes (T regs ) to combat ITM. The combination treatment of TNBCwith ISPN and αPD-L1-medaited immune checkpoint blockade therapy displays a synergistic effect on tumor regression, metastasis inhibition, and recurrence prevention. Overall, the ICG-templated nanomedicine may represent a robust nanoplatform for combination immunotherapy.

show abstract

“…Apart from pH‐responsive nanoparticles, MMP‐2‐sensitive nanoparticles were developed to enable tumor‐specific PDT‐triggered T‐cell activation. [ 50 ] Elevated MMP‐2 expression was reported in various cancer tissues, primarily driven by the imbalance between MMP‐2 and their natural inhibitors. [ 51 ] Wang et al developed MMP‐2‐sensitive nanoparticles to enable tumor‐specific delivery of anti‐PD‐L1 antibodies ( Figure A).…”

Section: Photodynamic Therapy and Its Immunomodulatory Effectmentioning

confidence: 99%

Section: Photodynamic Therapy and Its Immunomodulatory Effectmentioning

confidence: 99%

Recent Progress of Potentiating Immune Checkpoint Blockade with External Stimuli—an Industry Perspective

Saklatvala

Mittal

et al. 2020

Advanced Science

View full text Add to dashboard Cite

The past decade has seen the materialization of immune checkpoint blockade as an emerging approach to cancer treatment. However, the overall response and patient survival are still modest. Various efforts to study the “cancer immunogram” have highlighted complex biology that necessitates a multipronged approach. This includes increasing the antigenicity of the tumor, strengthening the immune infiltration in the tumor microenvironment, removing the immunosuppressive mechanisms, and reducing immune cell exhaustion. The coordination of these approaches, as well as the ability to enhance them through delivery, is evaluated. Due to their success in multiple preclinical models, external‐stimuli‐responsive nanoparticles have received tremendous attention. Several studies report success in distantly located tumor regression, metastases, and reoccurrence in preclinical mouse models. However, clinical translation in this space remains low. Herein, the recent advancement in external‐stimuli‐responsive nanoconstruct‐synergized immune checkpoint blockade is summarized, offering an industry perspective on the limitations of current academic innovations and discussing challenges in translation from a technical, manufacturing, and regulatory perspective. These limitations and challenges will need to be addressed to establish external‐stimuli‐based therapeutic strategies for patients.

show abstract

Engineering nanoparticles to locally activate T cells in the tumor microenvironment

Cited by 213 publications

References 62 publications

Codelivery of Anti‐PD‐1 Antibody and Paclitaxel with Matrix Metalloproteinase and pH Dual‐Sensitive Micelles for Enhanced Tumor Chemoimmunotherapy

Codelivery of Anti‐PD‐1 Antibody and Paclitaxel with Matrix Metalloproteinase and pH Dual‐Sensitive Micelles for Enhanced Tumor Chemoimmunotherapy

Enhancing Triple Negative Breast Cancer Immunotherapy by ICG‐Templated Self‐Assembly of Paclitaxel Nanoparticles

Recent Progress of Potentiating Immune Checkpoint Blockade with External Stimuli—an Industry Perspective

Contact Info

Product

Resources

About