tumor eradication
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2022 ◽  
Author(s):  
Johanna Theruvath ◽  
Marie Menard ◽  
Benjamin A. H. Smith ◽  
Miles H. Linde ◽  
Garry L. Coles ◽  
...  
Keyword(s):  

Small ◽  
2021 ◽  
pp. 2103528
Author(s):  
Bijiang Geng ◽  
Shuang Xu ◽  
Ping Li ◽  
Xiaokai Li ◽  
Fuling Fang ◽  
...  

2021 ◽  
Vol 9 (11) ◽  
pp. e003293
Author(s):  
Bram Van Den Eeckhout ◽  
Leander Huyghe ◽  
Sandra Van Lint ◽  
Elianne Burg ◽  
Stéphane Plaisance ◽  
...  

BackgroundClinical success of therapeutic cancer vaccines depends on the ability to mount strong and durable antitumor T cell responses. To achieve this, potent cellular adjuvants are highly needed. Interleukin-1β (IL-1β) acts on CD8+ T cells and promotes their expansion and effector differentiation, but toxicity and undesired tumor-promoting side effects hamper efficient clinical application of this cytokine.MethodsThis ‘cytokine problem’ can be solved by use of AcTakines (Activity-on-Target cytokines), which represent fusions between low-activity cytokine mutants and cell type-specific single-domain antibodies. AcTakines deliver cytokine activity to a priori selected cell types and as such evade toxicity and unwanted off-target side effects. Here, we employ subcutaneous melanoma and lung carcinoma models to evaluate the antitumor effects of AcTakines.ResultsIn this work, we use an IL-1β-based AcTakine to drive proliferation and effector functionality of antitumor CD8+ T cells without inducing measurable toxicity. AcTakine treatment enhances diversity of the T cell receptor repertoire and empowers adoptive T cell transfer. Combination treatment with a neovasculature-targeted tumor necrosis factor (TNF) AcTakine mediates full tumor eradication and establishes immunological memory that protects against secondary tumor challenge. Interferon-γ was found to empower this AcTakine synergy by sensitizing the tumor microenvironment to TNF.ConclusionsOur data illustrate that anticancer cellular immunity can be safely promoted with an IL-1β-based AcTakine, which synergizes with other immunotherapies for efficient tumor destruction.


2021 ◽  
Vol 118 (41) ◽  
pp. e2113028118
Author(s):  
Xuefeng Kan ◽  
Feng Zhang ◽  
Guanhui Zhou ◽  
Hongxiu Ji ◽  
Wayne Monsky ◽  
...  

The aim of this study was to develop an interventional optical imaging (OI) technique for intraprocedural guidance of complete tumor ablation. Our study employed four strategies: 1) optimizing experimental protocol of various indocyanine green (ICG) concentrations/detection time windows for ICG-based OI of tumor cells (ICG cells); 2) using the optimized OI to evaluate ablation-heat effect on ICG cells; 3) building the interventional OI system and investigating its sensitivity for differentiating residual viable tumors from nonviable tumors; and 4) preclinically validating its technical feasibility for intraprocedural monitoring of radiofrequency ablations (RFAs) using animal models with orthotopic hepatic tumors. OI signal-to-background ratios (SBRs) among preablation tumors, residual, and ablated tumors were statistically compared and confirmed by subsequent pathology. The optimal dose and detection time window for ICG-based OI were 100 μg/mL at 24 h. Interventional OI displayed significantly higher fluorescence signals of viable ICG cells compared with nonviable ICG cells (189.3 ± 7.6 versus 63.7 ± 5.7 au, P < 0.001). The interventional OI could differentiate three definitive zones of tumor, tumor margin, and normal surrounding liver, demonstrating significantly higher average SBR of residual viable tumors compared to ablated nonviable tumors (2.54 ± 0.31 versus 0.57 ± 0.05, P < 0.001). The innovative interventional OI technique permitted operators to instantly detect residual tumors and thereby guide repeated RFAs, ensuring complete tumor eradication, which was confirmed by ex vivo OI and pathology. In conclusion, we present an interventional oncologic technique, which should revolutionize the current ablation technology, leading to a significant advancement in complete treatment of larger or irregular malignancies.


2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Gustavo Ignacio Vázquez Cervantes ◽  
Dinora F. González Esquivel ◽  
Saúl Gómez-Manzo ◽  
Benjamín Pineda ◽  
Verónica Pérez de la Cruz

Glioblastoma (GBM) is the most common primary malignant brain tumor with a high mortality rate. The current treatment consists of surgical resection, radiation, and chemotherapy; however, the median survival rate is only 12–18 months despite these alternatives, highlighting the urgent need to find new strategies. The heterogeneity of GBM makes this tumor difficult to treat, and the immunotherapies result in an attractive approach to modulate the antitumoral immune responses favoring the tumor eradication. The immunotherapies for GMB including monoclonal antibodies, checkpoint inhibitors, vaccines, and oncolytic viruses, among others, have shown favorable results alone or as a multimodal treatment. In this review, we summarize and discuss promising immunotherapies for GBM currently under preclinical investigation as well as in clinical trials.


2021 ◽  
Vol 13 (610) ◽  
Author(s):  
Christian Hotz ◽  
Timothy R. Wagenaar ◽  
Friederike Gieseke ◽  
Dinesh S. Bangari ◽  
Michelle Callahan ◽  
...  

CCS Chemistry ◽  
2021 ◽  
pp. 1-23
Author(s):  
Chao Shi ◽  
Xiao Zhou ◽  
Qiancheng Zhao ◽  
Zhen Zhang ◽  
He Ma ◽  
...  

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Alexander A. Strait ◽  
Rachel A. Woolaver ◽  
Spencer C. Hall ◽  
Christian D. Young ◽  
Sana D. Karam ◽  
...  

AbstractTransforming growth factor beta (TGFβ) and programmed death-ligand 1 (PD-L1) are often overproduced in refractory squamous cell carcinoma (SCC). We examined spatial patterns of PD-L1+ cells in mouse and human SCCs and found that PD-L1 was primarily expressed on infiltrating leukocytes. Although combined TGFβ and PD-L1 blockade are undergoing cancer clinical trials, there are no predictive markers for therapeutic responders. To address this, we used both a small molecule TGFβ inhibitor in combination with anti-PD-L1 and a bifunctional fusion protein targeting both TGFβ and PD-L1 to treat mouse SCCs and found TGFβ inhibition enhanced PD-L1 blockade-induced tumor eradication in multiple tumor models. Furthermore, we identified distinct cell populations of responders and non-responders to bintrafusp alfa, with responders showing a shift toward a more immune-permissive microenvironment. The cellular and molecular signatures of responders versus non-responders to combined TGFβ and PD-L1 blockade provide important insights into future personalized immunotherapy in SCC.


Nanophotonics ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maryam Deinavizadeh ◽  
Alireza Kiasat ◽  
Nasrin Hooshmand ◽  
Mohammad Shafiei ◽  
Mohammad Sabaeian ◽  
...  

Abstract We designed novel biocompatible nanocomposite composed of gold nanorods coated with rod-like mesoporous silica SBA-15-SH particles, (GNRs@SBA-15-SH) as a new synergistic therapeutic device to deliver heat and drug to cancer cells for tumor eradication. For this purpose, doxorubicin (DOX) was loaded into GNRs@SBA-15-SH nanocomposites and studied their photothermal therapy, chemotherapy and the combined effect on the ablation of A549 cells in vitro using human lung cancer cells, A549. The results demonstrate the high photothermal efficacy of gold nanorods loaded into the nanocomposite, the thermo-responsive properties of GNRs@SBA-15-SH, the high loading capacity of DOX into the GNRs@SBA-15-SH and its biocompatibility. Synergistic chemo-photothermal of the GNRs@SBA-15-SH/DOX nanocomposite in the eradication of cancer cells under laser irradiation (808 nm), demonstrates the high potential of therapeutic efficacy of this combined therapy over monotherapies.


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