Magnetic field boosted ferroptosis-like cell death and responsive MRI using hybrid vesicles for cancer immunotherapy

The immune system can eradicate tumours, and several chemotherapy strategies have been reported to augment the immune system. Here, the authors report an exogenous magnetic field triggered strategy to boost Ferroptosis-like death and endow responsive MRI by using a biosafe hybrid core-shell vesicle for cancer therapy

Syngeneic N1-S1 Orthotopic Hepatocellular Carcinoma in Sprague Dawley Rat for the Development of Interventional Oncology-Based Immunotherapy: Survival Assay and Tumor Immune Microenvironment

Rodent HCC rat models provide advantages for interventional oncology (IO) based immunotherapy research compared to other established larger animal models or mice models. Rapid and predictable tumor growth and affordable costs permit the formation of a compelling preclinical model investigating novel IO catheter-directed therapies and local ablation therapies. Among orthotopic HCC models, the N1-S1 orthotopic HCC model has been involved in many research cases. Suboptimal tumor induction rates and potential spontaneous regression during tumor implantation procedures discouraged the use of the N1-S1 HCC model in IO-based immunotherapies. Here, N1-S1 HCC models were generated with a subcapsular implantation of two different number of N1-S1 cells using a mini-laporatomy. Tumor growth assay and immunological profiles which can preclinically evaluate the therapeutic efficacy of IO-based immunotherapy, were characterized. Finally, an N1-S1 HCC rat model generated with the proposed procedure demonstrated a representative immune suppressive HCC tumor environment without self-tumor regression. The optimized syngeneic N1-S1 HCC rat models represent an essential tool for pre-clinical evaluation of new IO immunotherapies for the treatment of HCC

Syngeneic N1-S1 Orthotopic Hepatocellular Carcinoma in Sprague Dawley Rat for the Development of Interventional Oncology-Based Immunotherapy: Survival Assay and Tumor Immune Microenvironment

Rodent HCC rat models provide advantages for interventional oncology (IO) based immunotherapy research compared to other established larger animal models or mice models. Rapid and predictable tumor growth and affordable costs permit the formation of a compelling preclinical model investigating novel IO catheter-directed therapies and local ablation therapies. Among orthotopic HCC models, the N1-S1 orthotopic HCC model has been involved in many research cases. Suboptimal tumor induction rates and potential spontaneous regression during tumor implantation procedures discouraged the use of the N1-S1 HCC model in IO-based immunotherapies. Here, N1-S1 HCC models were generated with a subcapsular implantation of two different number of N1-S1 cells using a mini-laporatomy. Tumor growth assay and immunological profiles which can preclinically evaluate the therapeutic efficacy of IO-based immunotherapy, were characterized. Finally, an N1-S1 HCC rat model generated with the proposed procedure demonstrated a representative immune suppressive HCC tumor environment without self-tumor regression. The optimized syngeneic N1-S1 HCC rat models represent an essential tool for pre-clinical evaluation of new IO immunotherapies for the treatment of HCC

Effective Delivery of Antigen−Encapsulin Nanoparticle Fusions to Dendritic Cells Leads to Antigen-Specific Cytotoxic T Cell Activation and Tumor Rejection

In cancer immunotherapy, robust and efficient activation of cytotoxic CD8⁺ T cell immune responses is a promising, but challenging task. Dendritic cells (DCs) are well-known professional antigen presenting cells that initiate and regulate antigen-specific cytotoxic CD8⁺ T cells that kill their target cells directly as well as secrete IFN-γ, a cytokine critical in tumor rejection. Here, we employed recently established protein cage nanoparticles, encapsulin (Encap), as antigenic peptide nanocarriers by genetically incorporating the OT-1 peptide of ovalbumin (OVA) protein to the three different positions of the Encap subunit. With them, we evaluated their efficacy in activating DC-mediated antigen-specific T cell cytotoxicity and consequent melanoma tumor rejection <i>in vivo</i>. DCs efficiently engulfed Encap and its variants (OT-1-Encaps), which carry antigenic peptides at different positions, and properly processed them within phagosomes. Delivered OT-1 peptides were effectively presented by DCs to naïve CD8⁺ T cells successfully, resulting in the proliferation of antigen-specific cytotoxic CD8⁺ T cells. OT-1-Encap vaccinations in B16-OVA melanoma tumor bearing mice effectively activated OT-1 peptide specific cytotoxic CD8⁺ T cells before or even after tumor generation, resulting in significant suppression of tumor growth in prophylactic as well as therapeutic treatments. A large number of cytotoxic CD8⁺ T cells that actively produce both intracellular and secretory IFN-γ were observed in tumor-infiltrating lymphocytes collected from B16-OVA tumor masses originally vaccinated with OT-1-Encap-C upon tumor challenges. The approaches we describe herein may provide opportunities to develop epitope-dependent vaccination systems that stimulate and/or modulate efficient and epitope-specific cytotoxic T cell immune responses in nonpathogenic diseases

Effective Delivery of Antigen-Encapsulin Nanoparticle Fusions to Dendritic Cells Leads to Antigen-Specific Cytotoxic T Cell Activation and Tumor Rejection

In cancer immunotherapy, robust and efficient activation of cytotoxic CD8+ T cell immune responses is a promising, but challenging task. Dendritic cells (DCs) are well-known professional antigen presenting cells that initiate and regulate antigen-specific cytotoxic CD8+ T cells that kill their target cells directly as well as secrete IFN-??, a cytokine critical in tumor rejection. Here, we employed recently established protein cage nanoparticles, encapsulin (Encap), as antigenic peptide nanocarriers by genetically incorporating the OT-1 peptide of ovalbumin (OVA) protein to the three different positions of the Encap subunit. With them, we evaluated their efficacy in activating DC-mediated antigen-specific T cell cytotoxicity and consequent melanoma tumor rejection in vivo. DCs efficiently engulfed Encap and its variants (OT-1-Encaps), which carry antigenic peptides at different positions, and properly processed them within phagosomes. Delivered OT-1 peptides were effectively presented by DCs to na&amp;iuml;ve CD8+ T cells successfully, resulting in the proliferation of antigen-specific cytotoxic CD8+ T cells. OT-1-Encap vaccinations in B16-OVA melanoma tumor bearing mice effectively activated OT-1 peptide specific cytotoxic CD8+ T cells before or even after tumor generation, resulting in significant suppression of tumor growth in prophylactic as well as therapeutic treatments. A large number of cytotoxic CD8+ T cells that actively produce both intracellular and secretory IFN-?? were observed in tumor-infiltrating lymphocytes collected from B16-OVA tumor masses originally vaccinated with OT-1-Encap-C upon tumor challenges. The approaches we describe herein may provide opportunities to develop epitope-dependent vaccination systems that stimulate and/or modulate efficient and epitope-specific cytotoxic T cell immune responses in nonpathogenic diseases.clos

Additional file 1 of Enhanced natural killer cell anti-tumor activity with nanoparticles mediated ferroptosis and potential therapeutic application in prostate cancer

Additional file 1: Figure S1. Ferumoxytol concentration dependent Cell viability changes of PC3 and NK92-MI. Ferumoxytol (0–160 μg/mL concentration) was added to each well and incubated for 72 h. Then, CCK-8 reagents were treated by the manufacturer’s instructions. Figure S2. Western blot analysis of PC-3 cells treated with various amounts of ferumoxytol (Fer (0 μg), Fer (50 μg), Fer (100 μg), and Fer (200 μg)) and quantification of relative bands of western blotting. Figure S3. Confocal microscope images of NK92-MI cells + PC3 prostate cancer cells + ferumoxytol treated with aPD-L1 or non-aPD-L1 (Target: attached PC3 cells, Effector: NK92-MI cells, E:T = 1:1, Blue: DAPI, and Green: NK92-MI). Figure S4. In vivo individual tumor growth curve of control group and each treatment group of NK cells, ferroptosis + NK cells, and NK cells + ferroptosis + aPD-L1 (n = 4~ 5 for each group). Figure S5. Gating strategies for immune cell

Selective and Effective Cancer Treatments using Target???Switchable Intracellular Bacterial Toxin Delivery Systems

Targeted cancer therapies have been extensively tested with the purpose to selectively suppress tumor growth and to avoid harming healthy tissue. However, failure to escape endosomes upon receptor???mediated endocytosis is a major obstacle limiting the efficacy of targeted cancer therapeutics. Here, novel target???switchable intracellular toxin delivery systems (TiTDS) are presented which use the catalytic and translocation domain of diphtheria toxin (dtA???T) as an intracellular toxin delivery platform and affibody molecules targeting human epidermal growth factor receptor 2 or epidermal growth factor receptor (HER2Afb or EGFRAfb) as target???specific ligands. The intracellular toxin delivery platform and the affibody molecules are genetically fused with SpyCatcher (SC) protein and SpyTag (ST) peptide, respectively, to generate dtA???T???SC and ST???HER2Afb or ST???EGFRAfb modules. These modules can be individually purified and post???translationally ligated to produce dtA???T/HER2Afb or dtA???T/EGFRAf. dtA???T/HER2Afb and dtA???T/EGFRAfb can selectively bind to their corresponding target cancer cells, efficiently enter the cells through receptor???mediated endocytosis, successfully escape endosomes, and release toxins into the cytosol. They exhibit high target???specific cytotoxicity in vitro and can significantly reduce tumor masses in vivo. TiTDS is a promising targeted cancer therapy platform because of its high target specificity, effective intracellular delivery of active toxins with improved therapeutic efficacy, and target switchability