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1.
Cytotherapy ; 24(3): 291-301, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34690063

RESUMO

BACKGROUND AIMS: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has shown great success in clinical trials. Programmed cell death 1 (PD-1)-expressing TILs show high specificity to autologous tumor cells. However, limited therapeutic efficiency is observed as a result of the tumor immune microenvironment (TIME). METHODS: Coupling PD-1+ex vivo-derived TILs with a monoclonal antibody against anti-PD-1 (aPD-1) reinvigorated the anti-tumor response of TILs against solid tumor without altering their high tumor targeting ability. RESULTS: Using a melanoma-bearing mouse model, PD-1+ TILs blocked with aPD-1 (PD-1+ TILs-aPD-1) exhibited a high capability for tumor targeting as well as improved anti-tumor response in TIME. Tumor growth was substantially delayed in the mice treated with PD-1+ TILs-aPD-1. CONCLUSIONS: The strategy utilizing TIL therapy coupled with immune checkpoint antibodies may extend to other therapeutic targets of ACT.


Assuntos
Imunoterapia Adotiva , Linfócitos do Interstício Tumoral , Receptor de Morte Celular Programada 1 , Animais , Apoptose , Linfócitos T CD8-Positivos , Terapia Baseada em Transplante de Células e Tecidos , Camundongos , Receptor de Morte Celular Programada 1/metabolismo , Microambiente Tumoral
2.
Adv Mater ; 34(1): e2106265, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34613627

RESUMO

Autoimmune diseases are the third most common disease influencing the quality of life of many patients. Here, a programmed cell death-ligand 1 + (PD-L1) mesenchymal stem cell (MSC) derived extracellular vesicles (MSC-sEVs-PD-L1) using lentivirus-mediated gene transfection technology is developed for reconfiguration of the local immune microenvironment of affected tissue in autoimmune diseases. MSC-sEVs-PD-L1 exhibits an impressive ability to regulate various activated immune cells to an immunosuppressed state in vitro. More importantly, in dextran sulfate sodium-induced ulcerative colitis (UC) and imiquimod-induced psoriasis mouse models, a significantly high accumulation of MSC-sEVs-PD-L1 is observed in the inflamed tissues compared to the PD-L1+ MSCs. Therapeutic efficiency in both UC and psoriasis mouse disease models is demonstrated using MSC-sEVs-PD-L1 to reshape the inflammatory ecosystem in the local immune context. A technology is developed using MSC-sEVs-PD-L1 as a natural delivery platform for autoimmune diseases treatment with high clinical potential.


Assuntos
Doenças Autoimunes , Vesículas Extracelulares , Células-Tronco Mesenquimais , Animais , Doenças Autoimunes/metabolismo , Doenças Autoimunes/terapia , Antígeno B7-H1/genética , Ecossistema , Vesículas Extracelulares/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Qualidade de Vida
3.
Sci Adv ; 6(47)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33219021

RESUMO

Dendritic cell (DC) modification to enhance antigen presentation is a valuable strategy in cancer immune therapy. Other than focusing on regulating interactions between DC and antigens, we intend to promote cell interactions between DC and T cell by cell surface engineering. T cell activation is greatly improved and generates higher tumor toxicity with the aid of the synthetic glycopolymer modified on the DC surface, although the glycopolymer alone shows no effect. The great promotion of DC-T cell attraction is revealed by cell image tracking in terms of both frequency and duration of contacts. Our findings provide a new method of T cell activation by these engineered "sweet DCs." This strategy is beneficial for developing more efficient DC-based vaccines.

4.
Small ; 16(28): e2000589, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32521098

RESUMO

The emergence of drug-resistant bacteria and easy recurrence has been challenging in the clinical treatment of skin abscesses resulting from bacterial infections (e.g., by Staphylococcus aureus (S. aureus)). Herein, an antibacterial nanoagent capable of modulating the abscess microenvironment is designed to enhance photodynamic treatment of skin abscesses, and subsequently activate the immune system to effectively prevent abscess recurrence. In the system, manganese dioxide nanoparticles (MnO2 NPs) with high catalytic reactivity toward H2 O2 are modified with photosensitizer chlorine e6 (Ce6) and coated with polyethylene glycol (PEG). The obtained Ce6@MnO2 -PEG NPs, by triggering the decomposition of lesion endogenous H2 O2 , are able to effectively relieve the hypoxic abscess microenvironment during S. aureus infection. The light-triggered photodynamic bacterial killing effect could thus be remarkably enhanced, resulting in effective in vivo therapy of S. aureus-induced skin abscesses. Interestingly, a notable pathogen-specific immunological memory effect against future infection by the same species of bacteria is elicited after such treatment, owing to the release of bacterial antigens post photodynamic therapy (PDT) together with the adjuvant-like function of manganese ions to activate the host immune system. This work thus presents a new type of photodynamic nanoagent particularly promising for highly effective light-triggered abscess treatment and prevention of abscess recurrence.


Assuntos
Nanopartículas , Fotoquimioterapia , Abscesso/tratamento farmacológico , Animais , Compostos de Manganês , Camundongos , Óxidos , Fármacos Fotossensibilizantes , Staphylococcus aureus
5.
Biomaterials ; 224: 119490, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31542515

RESUMO

Tumor ablation therapies provide a minimally invasive approach to treat cancer. However, inhibition of cancer metastasis and recurrence after ablation is still a challenge in clinical trials. Here, we propose a strategy using combinatorial thermal ablation, adjuvants and immune checkpoint blockade (ICB) to inhibit metastatic tumor and recurrence via antitumor immune responses post tumor thermal ablation, which are frequently used in the clinic. Furthermore, a strong immune memory against cancer was observed 80 days after the primary tumor was ablated. Considering that all components in our design are approved by Food and Drug Administration (FDA), we provide a strategy based on clinically used cancer treatment technique that is promising in clinical translation.


Assuntos
Adjuvantes Imunológicos/farmacologia , Hipertermia Induzida , Imunoterapia , Nanopartículas/química , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias/terapia , Animais , Linhagem Celular Tumoral , Células Dendríticas/metabolismo , Feminino , Memória Imunológica/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Neoplasias/imunologia , Neoplasias/patologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Microambiente Tumoral/efeitos dos fármacos
6.
J Control Release ; 304: 233-241, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31071371

RESUMO

Cancer local physical therapy (PT) by using heat, cold, electrical stimulation, irradiation or ultrasound to treat tumor is accepted as alternative choice for cancer patients. However, local recurrence and metastasis after such treatments remains to be the major cause of treatment failure and mortality. Therefore, it is necessary to develop a therapeutic strategy to inhibit local recurrence and metastasis. Inspired by the excellent inflammatory targeting ability of platelets, here we expect that the monoclonal antibody against programmed-death ligand 1 (aPDL1) engineered platelets could inhibit tumor local recurrence effectively, by facilitating transport of anti-PD-L1 antibodies to the ablated area with residue tumors. Using triple-negative breast carcinomas (4T1) bearing mouse model, we proved that antibody-coupled platelets could effectively target incompletely ablated tumor with thermal ablation (TA). We found the release of anti-PD-L1 can be triggered upon the platelets activation, together with many pro-inflammatory cytokines. The release of anti-PD-L1 is likely due to the dissociation of platelets upon the activation. Our findings approved that our platelet-based platform could facilitate the delivery of immune checkpoint antibody to tumor residues and remarkably prevent tumor recurrence after ablation. Moreover, this platelet-based delivery strategy may be extended to the targeted delivery of therapeutics post other types of local therapies including photodynamic therapy, high-intensity-focused-ultrasound ablation therapy, and even radiotherapy.


Assuntos
Anticorpos Monoclonais/imunologia , Antígeno B7-H1/imunologia , Plaquetas/metabolismo , Neoplasias Mamárias Experimentais/terapia , Animais , Anticorpos Monoclonais/administração & dosagem , Citocinas/imunologia , Feminino , Imunoterapia/métodos , Neoplasias Mamárias Experimentais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Recidiva Local de Neoplasia , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/terapia
7.
J Environ Sci (China) ; 14(1): 102-7, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11887304

RESUMO

According to the practice researching and formulating "The Oil Spill Contingency Plan of South Chinese Sea", this paper analyses and discusses the structure, functions and main contents of marine oil spill contingency planning, programs the organizing and commanding system and emergency response system, and advances the planning and researching method to coordinate comprehensively and to design practically the detailed emergency response steps until to formulate the ease operating programs for the plan implementation(PPI) and the PPI to apply high-techniques supporting emergency administrations and response.


Assuntos
Planejamento em Desastres , Petróleo , Poluição da Água , Meio Ambiente , Biologia Marinha
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