scholarly journals Irreversible Electroporation: An Emerging Immunomodulatory Therapy on Solid Tumors

2022 ◽  
Vol 12 ◽  
Author(s):  
Nana Zhang ◽  
Zhuoqun Li ◽  
Xuan Han ◽  
Ziyu Zhu ◽  
Zhujun Li ◽  
...  
Keyword(s):  
Immune Response ◽  
Solid Tumors ◽  
Tumor Vaccine ◽  
Malignant Tumors ◽  
Irreversible Electroporation ◽  
Immunomodulatory Therapy ◽  
Research Progress ◽  
Current Status ◽  
Tumor Treatment ◽  
Electric Pulses

Irreversible electroporation (IRE), a novel non-thermal ablation technique, is utilized to ablate unresectable solid tumors and demonstrates favorable safety and efficacy in the clinic. IRE applies electric pulses to alter the cell transmembrane voltage and causes nanometer-sized membrane defects or pores in the cells, which leads to loss of cell homeostasis and ultimately results in cell death. The major drawbacks of IRE are incomplete ablation and susceptibility to recurrence, which limit its clinical application. Recent studies have shown that IRE promotes the massive release of intracellular concealed tumor antigens that become an “in-situ tumor vaccine,” inducing a potential antitumor immune response to kill residual tumor cells after ablation and inhibiting local recurrence and distant metastasis. Therefore, IRE can be regarded as a potential immunomodulatory therapy, and combined with immunotherapy, it can exhibit synergistic treatment effects on malignant tumors, which provides broad application prospects for tumor treatment. This work reviewed the current status of the clinical efficacy of IRE in tumor treatment, summarized the characteristics of local and systemic immune responses induced by IRE in tumor-bearing organisms, and analyzed the specific mechanisms of the IRE-induced immune response. Moreover, we reviewed the current research progress of IRE combined with immunotherapy in the treatment of solid tumors. Based on the findings, we present deficiencies of current preclinical studies of animal models and analyze possible reasons and solutions. We also propose possible demands for clinical research. This review aimed to provide theoretical and practical guidance for the combination of IRE with immunotherapy in the treatment of malignant tumors.

Feasibility Study for Applying Irreversible Electroporation to the Treatment of Breast Cancer

2009 ◽  
Author(s):  
Robert E. Neal ◽  
Ravi Singh ◽  
Suzy Torti ◽  
Rafael V. Davalos
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Extracellular Matrix ◽  
Numerical Modeling ◽  
Cell Membrane ◽  
Irreversible Electroporation ◽  
Short Length ◽  
Tissue Ablation ◽  
Electric Pulses ◽  
A Cell

Non-thermal irreversible electroporation (IRE) is a new, minimally invasive, localized tissue ablation technique [1]. The procedure uses electrodes to deliver short-length, high voltage electric pulses to destabilize a cell membrane, leading to the creation of nanopores. When the pulses are strong enough, the cell cannot repair the damage and dies [2]. It has been shown that substantial volumes of tissue and cutaneous tumors may be ablated in a non-thermal manner using irreversible electroporation [1, 3]. In addition, this procedure may be predicted by numerical modeling, promotes an immune response, leaves the extracellular matrix intact, does not affect nerves, may be monitored in real-time, and preserves tissue vasculature [2–5].

scholarly journals Analysis of damage-associated molecular pattern molecules due to electroporation of cells in vitro

2020 ◽  
Vol 54 (3) ◽  
pp. 317-328 ◽  
Author(s):  
Tamara Polajzer ◽  
Tomaz Jarm ◽  
Damijan Miklavcic
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Uric Acid ◽  
Chinese Hamster Ovary Cells ◽  
Irreversible Electroporation ◽  
Time Interval ◽  
Electric Pulses ◽  
Cell Death Pathway ◽  
Molecular Pattern

AbstractBackgroundTumor cells can die via immunogenic cell death pathway, in which damage-associated molecular pattern molecules (DAMPs) are released from the cells. These molecules activate cells involved in the immune response. Both innate and adaptive immune response can be activated, causing a destruction of the remaining infected cells. Activation of immune response is also an important component of tumor treatment with electrochemotherapy (ECT) and irreversible electroporation (IRE). We thus explored, if and when specific DAMPs are released as a consequence of electroporation in vitro.Materials and methodsIn this in vitro study, 100 μs long electric pulses were applied to a suspension of Chinese hamster ovary cells. The release of DAMPs – specifically: adenosine triphosphate (ATP), calreticulin, nucleic acids and uric acid was investigated at different time points after exposing the cells to electric pulses of different amplitudes. The release of DAMPs was statistically correlated with cell permeabilization and cell survival, e.g. reversible and irreversible electroporation.ResultsIn general, the release of DAMPs increases with increasing pulse amplitude. Concentration of DAMPs depend on the time interval between exposure of the cells to pulses and the analysis. Concentrations of most DAMPs correlate strongly with cell death. However, we detected no uric acid in the investigated samples.ConclusionsRelease of DAMPs can serve as a marker for prediction of cell death. Since the stability of certain DAMPs is time dependent, this should be considered when designing protocols for detecting DAMPs after electric pulse treatment.

Practical consensus recommendations - Current role of immune response evaluation criteria in solid tumors criteria in the management of cancer patients receiving immunotherapy

2019 ◽  
Vol 4 ◽  
pp. 21-23
Author(s):  
Purvish M. Parikh ◽  
T. P. Sahoo ◽  
Randeep Singh ◽  
Bahl Ankur ◽  
Talvar Vineet ◽  
...  
Keyword(s):  
Immune Response ◽  
Solid Tumors ◽  
Evaluation Criteria ◽  
Supporting Evidence ◽  
Response Evaluation ◽  
Consensus Recommendation ◽  
Current Role ◽  
New Class ◽  
Response Evaluation Criteria

Response evaluation criteria in solid tumors (RECIST) are a method used to evaluate and document the response to cancer treatment in solid tumors. The availability of a new class of immuneoncology drugs has resulted in the need to modify RECIST criteria methodology. The first leadership immuno-oncology network (LION) master course brought together experts in oncology and immuno-oncology. Six questions were put to the experts and their opinion, supporting evidence, and experience were discussed to arrive at a practical consensus recommendation. n this nascent field, the availability of a practical consensus recommendation developed by experts in the field is of immense value to the community oncologist and other health-care consultants.

scholarly journals NIR responsive tumor vaccine in situ for photothermal ablation and chemotherapy to trigger robust antitumor immune responses

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lirong Zhang ◽  
Jingjing Zhang ◽  
Lixia Xu ◽  
Zijian Zhuang ◽  
Jingjin Liu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Vaccine ◽  
Oxidative Polymerization ◽  
Delivery Mode ◽  
Tumor Treatment ◽  
One Pot ◽  
Photothermal Ablation ◽  
Prolonged Retention ◽  
The One

Abstract Background Therapeutic tumor vaccine (TTV) that induces tumor-specific immunity has enormous potentials in tumor treatment, but high heterogeneity and poor immunogenicity of tumor seriously impair its clinical efficacy. Herein, a novel NIR responsive tumor vaccine in situ (HA-PDA@IQ/DOX HG) was prepared by integrating hyaluronic acid functionalized polydopamine nanoparticles (HA-PDA NPs) with immune adjuvants (Imiquimod, IQ) and doxorubicin (DOX) into thermal-sensitive hydrogel. Results HA-PDA@IQ NPs with high photothermal conversion efficiency (41.2%) and T1-relaxation efficiency were using HA as stabilizer by the one-pot oxidative polymerization. Then, HA-PDA@IQ loaded DOX via π-π stacking and mixed with thermal-sensitive hydrogel to form the HA-PDA@IQ/DOX HG. The hydrogel-confined delivery mode endowed HA-PDA@IQ/DOX NPs with multiple photothermal ablation performance once injection upon NIR irradiation due to the prolonged retention in tumor site. More importantly, this mode enabled HA-PDA@IQ/DOX NPs to promote the DC maturation, memory T cells in lymphatic node as well as cytotoxic T lymphocytes in spleen. Conclusion Taken together, the HA-PDA@IQ/DOX HG could be served as a theranostic tumor vaccine for complete photothermal ablation to trigger robust antitumor immune responses.

scholarly journals WEE1i and ATRi trigger STING‐dependent immune response and enhance tumor treatment efficacy through PD‐L1 blockade

2021 ◽  
Author(s):  
Xue Wu ◽  
Xiaoyan Kang ◽  
Xiaoxiao Zhang ◽  
Wan Xie ◽  
Yue Su ◽  
...  
Keyword(s):  
Immune Response ◽  
Treatment Efficacy ◽  
Tumor Treatment

scholarly journals Integration of Digital Economy and Circular Economy: Current Status and Future Directions

2021 ◽  
Vol 13 (13) ◽  
pp. 7217
Author(s):  
Zhen Liu ◽  
Jing Liu ◽  
Mohamed Osmani
Keyword(s):  
Circular Economy ◽  
Digital Technology ◽  
Global Economy ◽  
Digital Economy ◽  
Research Field ◽  
Research Progress ◽  
Current Status ◽  
Future Research ◽  
Disruptive Effect ◽  
The European Union

Circular economy (CE) is a concept actively advocated by the European Union (EU), China, Japan, and the United Kingdom. At present, CE is considered to grant the most traction for companies to achieve sustainable development. However, CE is still rarely adopted by enterprises. As the backbone of the fourth industrial revolution, the digital economy (DE) is considered to have a disruptive effect. Studies have shown that digital technology has great potential in promoting the development of CE. Especially during the COVID-19 epidemic that has severely negatively affected the global economy, environment, and society, CE and DE are receiving high attention from policy makers, practitioners, and scholars around the world. However, the integration of CE and digital technology is a small and rapidly developing research field that is still in its infancy. Although there is a large amount of research in the fields of CE and DE, respectively, there are few studies that look into integrating these two fields. Therefore, the purpose of this paper is to explore the research progress and trends of the integration of CE and DE, and provide an overview for future research. This paper adopts a bibliometric research method, employs the Web of Science database as its literature source, and uses VOSviewer visual software to carry out keyword co-occurrence analysis, which focuses on publication trends, journal sources, keyword visualization, multidisciplinary areas, life cycle stages, and application fields.

scholarly journals COVID-19 Immune Response, Complications, and Current Status

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 532-532
Author(s):  
Albert Shaw
Keyword(s):  
Immune Response ◽  
Current Status

132 CAR macrophages (CAR-M) elicit a systemic anti-tumor immune response and synergize with PD1 blockade in immunocompetent mouse models of HER2+ solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A145-A145
Author(s):  
Stefano Pierini ◽  
Rashid Gabbasov ◽  
Linara Gabitova ◽  
Yumi Ohtani ◽  
Michael Klichinsky
Keyword(s):  
Immune Response ◽  
Overall Survival ◽  
Animal Model ◽  
T Cell ◽  
Cancer Cells ◽  
Solid Tumors ◽  
Tumor Model ◽  
Epitope Spreading ◽  
Mhc I ◽  
Single Tumor

BackgroundDespite the remarkable efficacy achieved by CAR-T therapy in hematologic malignancies, application in solid tumors has been challenging. We previously developed human CAR-M and demonstrated that adoptive cell transfer of CAR-M into xenograft models of human cancer controls tumor progression and improves overall survival [1]. Given that CAR-M are professional antigen presenting cells, we developed an immunocompetent animal model to evaluate the potential for induction of a systemic anti-tumor immune response.MethodsMurine bone marrow-derived macrophages were engineered to express an anti-HER2 CAR using the chimeric adenoviral vector Ad5f35. CAR-M were phenotypically and functionally evaluated in vitro and in syngeneic models. To evaluate CAR-M efficacy in an immunocompetent animal model, BALB/c mice were engrafted with CT26-HER2+ tumors (single-tumor model) and were treated with intratumoral CAR-HER2 or untransduced (UTD) macrophages. To evaluate epitope spreading, we simultaneously engrafted BALB/c mice with CT26-HER2+ and CT26-Wt tumors on opposite flanks (dual-tumor model), and treated mice with CAR-M or controls into the CT26-HER2+ tumor only. Peripheral and tumor-infiltrating immune cells were phenotypically and functionally characterized.ResultsIn addition to efficient gene delivery, Ad5f35 transduction promoted a pro-inflammatory (M1) phenotype in murine macrophages. CAR-M, but not control UTD macrophages, phagocytosed HER2+ target cancer cells. Anti-HER2 CAR-M eradicated HER2+ murine CT26 colorectal and human AU-565 breast cancer cells in a dose-dependent manner. CAR-M increased MHC-I and MHC-II expression on tumor cells and promoted tumor-associated antigen presentation and T cell activation. In vivo, CAR-M treatment led to tumor regression and improved overall survival in the CT26-HER2+ single-tumor model. In the dual-tumor model, CAR-M treatment cleared 75% of CT26-HER2+ tumors and inhibited the growth rate of contralateral CT26-WT tumors, demonstrating an abscopal effect. CAR-M treatment led to increased infiltration of intratumoral CD4+ and CD8+ T, NK, and dendritic cells – as well as an increase in T cell responsiveness to the CT26 MHC-I antigen gp70, indicating enhanced epitope spreading. Given the impact CAR-M had on endogenous T-cell immunity, we evaluated the combination of CAR-M and anti-PD1 in the CT26-HER2 model and found that the combination further enhanced tumor control and overall survival.ConclusionsThese results demonstrate that CAR-M therapy induces epitope spreading via activation of endogenous T cells, orchestrating a systemic immune response against solid tumors. Moreover, our findings provide rationale for the combination of CAR-M with immune checkpoint inhibitors. The anti-HER2 CAR-M CT-0508 will be evaluated in an upcoming Phase I clinical trial.ReferenceKlichinsky M, Ruella M, Shestova O, et al. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat Biotechnol 2020;38(8):947–953.

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