Abstract 2221: Combining irreversible electroporation with TLR7 and CD40 agonists confers systemic anti-tumor immunity in a murine pancreatic cancer model

Author(s):  
Jayanth Surya Narayanan Shankara Narayanan ◽  
Diego Vicente ◽  
Partha Ray ◽  
Thomas Whisenant ◽  
Rebekah White
2019 ◽  
Vol 7 (10) ◽  
pp. 1714-1726 ◽  
Author(s):  
Jayanth S. Shankara Narayanan ◽  
Partha Ray ◽  
Tomoko Hayashi ◽  
Thomas C. Whisenant ◽  
Diego Vicente ◽  
...  

2021 ◽  
Vol 10 (1) ◽  
pp. 1875638
Author(s):  
Jia Yang ◽  
Aydin Eresen ◽  
Junjie Shangguan ◽  
Quanhong Ma ◽  
Vahid Yaghmai ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2862
Author(s):  
Rasmus V. Flak ◽  
Rune V. Fisker ◽  
Niels H. Bruun ◽  
Mogens T. Stender ◽  
Ole Thorlacius-Ussing ◽  
...  

(1) Background: Irreversible electroporation (IRE) is a nonthermal ablation technique that is being studied in nonmetastatic pancreatic cancer (PC). Most published studies use imaging outcomes as an efficacy endpoint, but imaging interpretation can be difficult and has yet to be correlated with survival. The aim of this study was to examine the correlation of imaging endpoints with survival in a cohort of IRE-treated PC patients. (2) Methods: Several imaging endpoints were examined before and after IRE on 18F-fluorodeoxyglucose positron emission tomography (PET) with computed tomography. Separate analyses were performed at the patient and lesion levels. Mortality rate (MR) ratios for imaging endpoints after IRE were estimated. (3) Results: Forty-one patients were included. Patient-level analysis revealed that progressive disease (PD), as defined by RECIST 1.1, is correlated with a higher MR at all time intervals, but PD, as defined by EORTC PET response criteria, is only correlated with the MR in the longest interval. No correlation was found between PD, as defined by RECIST, and the MR in the lesion-level analysis. (4) Conclusions: Patient-level PD, as defined by RECIST, was correlated with poorer survival after IRE ablation, whereas no correlations were observed in the lesion-level analyses. Several promising lesion-level outcomes were identified.


2021 ◽  
Vol 10 (8) ◽  
pp. 1609
Author(s):  
Zainab L. Rai ◽  
Roger Feakins ◽  
Laura J. Pallett ◽  
Derek Manas ◽  
Brian R. Davidson

Locally advanced pancreatic cancer (LAPC) accounts for 30% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a novel cancer treatment that may improve survival and quality of life in LAPC. This narrative review will provide a perspective on the clinical experience of pancreas IRE therapy, explore the evidence for the mode of action, assess treatment complications, and propose strategies for augmenting IRE response. A systematic search was performed using PubMed regarding the clinical use and safety profile of IRE on pancreatic cancer, post-IRE sequential histological changes, associated immune response, and synergistic therapies. Animal data demonstrate that IRE induces both apoptosis and necrosis followed by fibrosis. Major complications may result from IRE; procedure related mortality is up to 2%, with an average morbidity as high as 36%. Nevertheless, prospective and retrospective studies suggest that IRE treatment may increase median overall survival of LAPC to as much as 30 months and provide preliminary data justifying the well-designed trials currently underway, comparing IRE to the standard of care treatment. The mechanism of action of IRE remains unknown, and there is a lack of data on treatment variables and efficiency in humans. There is emerging data suggesting that IRE can be augmented with synergistic therapies such as immunotherapy.


Pancreas ◽  
2004 ◽  
Vol 29 (4) ◽  
pp. 320-323 ◽  
Author(s):  
Ajit T. Abraham ◽  
Sudeep R. Shah ◽  
Brian R. Davidson

2015 ◽  
Vol 23 (5) ◽  
pp. 1736-1743 ◽  
Author(s):  
Michael D. Kluger ◽  
Irene Epelboym ◽  
Beth A. Schrope ◽  
Krishnaraj Mahendraraj ◽  
Elizabeth M. Hecht ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alissa Hendricks-Wenger ◽  
Kenneth N. Aycock ◽  
Margaret A. Nagai-Singer ◽  
Sheryl Coutermarsh-Ott ◽  
Melvin F. Lorenzo ◽  
...  

AbstractNew therapies to treat pancreatic cancer are direly needed. However, efficacious interventions lack a strong preclinical model that can recapitulate patients’ anatomy and physiology. Likewise, the availability of human primary malignant tissue for ex vivo studies is limited. These are significant limitations in the biomedical device field. We have developed RAG2/IL2RG deficient pigs using CRISPR/Cas9 as a large animal model with the novel application of cancer xenograft studies of human pancreatic adenocarcinoma. In this proof-of-concept study, these pigs were successfully generated using on-demand genetic modifications in embryos, circumventing the need for breeding and husbandry. Human Panc01 cells injected subcutaneously into the ears of RAG2/IL2RG deficient pigs demonstrated 100% engraftment with growth rates similar to those typically observed in mouse models. Histopathology revealed no immune cell infiltration and tumor morphology was highly consistent with the mouse models. The electrical properties and response to irreversible electroporation of the tumor tissue were found to be similar to excised human pancreatic cancer tumors. The ample tumor tissue produced enabled improved accuracy and modeling of the electrical properties of tumor tissue. Together, this suggests that this model will be useful and capable of bridging the gap of translating therapies from the bench to clinical application.


Pancreatology ◽  
2017 ◽  
Vol 17 (4) ◽  
pp. S54-S55
Author(s):  
Cintia Morioka ◽  
Jose Pinhata Otoch ◽  
Marcel Cerqueira Cesar Machado ◽  
Joelmir Lucena Veiga Veiga ◽  
Nixon Alves Pereira ◽  
...  

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Chelsea M. Edelblute ◽  
James Hornef ◽  
Niculina I. Burcus ◽  
Thomas Norman ◽  
Stephen J. Beebe ◽  
...  

1977 ◽  
Vol 2 (4-5) ◽  
pp. 233-237 ◽  
Author(s):  
Parviz Pour ◽  
Jürgen Althoff ◽  
Friederich W. Krüger ◽  
Ulrich Mohr

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