scholarly journals Viral oncolytic immunotherapy in the war on cancer: Infection control considerations

2019 ◽  
Vol 40 (3) ◽  
pp. 350-354 ◽  
Author(s):  
Elizabeth V. Robilotti ◽  
Asmita Kumar ◽  
Michael S. Glickman ◽  
Mini Kamboj
Keyword(s):  
Infection Control ◽  
Horizontal Transmission ◽  
Oncolytic Viruses ◽  
Novel Therapy ◽  
New Agents ◽  
Fda Approval ◽  
Ongoing Care ◽  
Infection Preventionists ◽  
Current Mechanism

AbstractOncolytic viral immunotherapy is an emerging treatment modality for cancer that exploits in vivo replication and other viral properties to enhance immune killing of malignant cells. The potential for horizontal transmission of native or engineered oncolytic viruses creates several unique infection control challenges. In 2015, talimogene laherparepvec (TVEC) became the first agent in this class to gain FDA approval for treatment of melanoma, and several others are being developed. Although some data on the transmissibility of TVEC are available from clinical studies, the aftermarket or real-world experience remains limited. We conducted a PUBMED-based search of the medical literature focusing on the safety and risk of TVEC transmission to close contacts including healthcare workers. The findings are summarized in this review and are intended to provide infection preventionists with practical guidance on handling issues related to administration and care of patients receiving TVEC. Additionally, we describe the current mechanism for evaluating the risk related to similar new agents entering clinical trials at our institution. Development of standarized approaches for the safe administration and precautions for ongoing care, especially in immunocompromised patients, are essential to support the broad adoption of this novel therapy.

New agents for thromboprotection

2015 ◽  
Vol 35 (04) ◽  
pp. 338-350 ◽  
Author(s):  
L. Labberton ◽  
E. Kenne ◽  
T. Renné
Keyword(s):  
Current Knowledge ◽  
Thrombus Formation ◽  
Coagulation Cascade ◽  
Factor Xii ◽  
Bleeding Tendency ◽  
New Agents ◽  
Mechanistic Basis ◽  
Normal Hemostasis ◽  
Coagulation Pathway

SummaryBlood coagulation is essential for hemostasis, however excessive coagulation can lead to thrombosis. Factor XII starts the intrinsic coagulation pathway and contact-induced factor XII activation provides the mechanistic basis for the diagnostic aPTT clotting assay. Despite its function for fibrin formation in test tubes, patients and animals lacking factor XII have a completely normal hemostasis. The lack of a bleeding tendency observed in factor XII deficiency states is in sharp contrast to deficiencies of other components of the coagulation cascade and factor XII has been considered to have no function for coagulation in vivo. Recently, experimental animal models showed that factor XII is activated by an inorganic polymer, polyphosphate, which is released from procoagulant platelets and that polyphosphate-driven factor XII activation has an essential role in pathologic thrombus formation. Cumulatively, the data suggest to target polyphosphate, factor XII, or its activated form factor XIIa for anticoagulation. As the factor XII pathway specifically contributes to thrombosis but not to hemostasis, interference with this pathway provides a unique opportunity for safe anticoagulation that is not associated with excess bleeding.The review summarizes current knowledge on factor XII functions, activators and inhibitors.

scholarly journals Experimental Horizontal Transmission of Enterospora nucleophila (Microsporea: Enterocytozoonidae) in Gilthead Sea Bream (Sparus aurata)

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 362
Author(s):  
Amparo Picard-Sánchez ◽  
M. Carla Piazzon ◽  
Itziar Estensoro ◽  
Raquel Del Pozo ◽  
Nahla Hossameldin Ahmed ◽  
...  
Keyword(s):  
Sparus Aurata ◽  
Horizontal Transmission ◽  
Infected Fish ◽  
Gilthead Sea Bream ◽  
Sea Bream ◽  
Target Tissue ◽  
Farmed Fish ◽  
Infection Level ◽  
Available Information

Enterospora nucleophila is a microsporidian enteroparasite that infects mainly the intestine of gilthead sea bream (Sparus aurata), leading to an emaciative syndrome. Thus far, the only available information about this infection comes from natural outbreaks in farmed fish. The aim of the present study was to determine whether E. nucleophila could be transmitted horizontally using naturally infected fish as donors, and to establish an experimental in vivo procedure to study this host–parasite model without depending on natural infections. Naïve fish were exposed to the infection by cohabitation, effluent, or intubated either orally or anally with intestinal scrapings of donor fish in four different trials. We succeeded in detecting parasite in naïve fish in all the challenges, but the infection level and the disease signs were always milder than in donor fish. The parasite was found in peripheral blood of naïve fish at 4 weeks post-challenge (wpc) in oral and effluent routes, and up to 12 wpc in the anal transmission trial. Molecular diagnosis detected E. nucleophila in other organs besides intestine, such as gills, liver, stomach or heart, although the intensity was not as high as in the target tissue. The infection tended to disappear through time in all the challenge routes assayed, except in the anal infection route.

290 Cytokine and immune subset signatures in patients with various solid and hematological malignancies treated with oncolytic vaccinia virus delivered by autologous stromal vascular fraction cells

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A317-A317
Author(s):  
Dobrin Draganov ◽  
Antonio Santidrian ◽  
Ivelina Minev ◽  
Duong Nguyen ◽  
Dmitriy Zamarin ◽  
...  
Keyword(s):  
T Cell ◽  
Vaccinia Virus ◽  
Stromal Vascular Fraction ◽  
Oncolytic Viruses ◽  
Multiparameter Flow Cytometry ◽  
Viral Dna ◽  
Cell Responses ◽  
The Impact ◽  
Immune Subset

BackgroundThe development of oncolytic viruses for the treatment of cancer has been significantly hampered by their rapid clearance in circulation due to complement and antibody-mediated neutralization. In our recent first-in-human Phase I clinical trial, we evaluated the safety and feasibility of our approach to enhance virus delivery and improve tumor targeting by utilizing an autologous stromal vascular fraction (SVF) based cell delivery system. Patient sample analysis demonstrated that patients could be stratified based on the level of vaccinia virus amplification in vivo, as evidenced by analysis of persistent viral DNA in the blood.MethodsIn the current study, we evaluated the immunomodulatory potential of vaccinia virus delivered by autologous stromal vascular fraction (SVF)-derived cells and attempted to identify immunological correlates of successful vaccinia virus amplification in vivo. To this end, we performed an extensive time-course analysis of cytokines in patients‘ plasma as well as various peripheral blood immune subpopulations using Luminex multi-analyte profiling and multiparameter flow cytometry, respectively. We also analyzed the impact of this therapeutic approach on the innate and adaptive immune subpopulations, including NK cells, myeloid cells, as well as effector, regulatory and memory T cells.ResultsTherapy with SFV-delivered oncolytic vaccinia virus induced a coordinated activation of cytokine, T cell and NK cell responses in patients as early as 1 day after treatment, which peaked around 1-week and lasted for up to 1-month post treatment. The ability of the oncolytic virus to effectively amplify in cancer patients correlated with significant changes of multiple innate (NK) and adaptive (T cell) immunological parameters. Interestingly, patient stratification into groups with transient versus persistent viral DNA was linked to opposing and mutually exclusive patterns of robust activation of NK versus T cell responses, respectively. Our study also identified intriguing cytokine and immune subset frequency signatures present at baseline and associated with successful amplification and persistence of oncolytic vaccinia virus in vivo.ConclusionsOverall, this study establishes the timeline of treatment-related immunological changes and identifies biomarkers present at baseline and potential immunological correlates associated with the persistence of virus amplification in vivo. Therefore, our findings provide new insights into the role of interpatient immunological variability and will contribute to the proper evaluation of the therapeutic potency of oncolytic virotherapy in future clinical trials.

scholarly journals The importance of imaging strategies for pre-clinical and clinical in vivo distribution of oncolytic viruses

2018 ◽  
Vol Volume 7 ◽  
pp. 25-35 ◽  
Author(s):  
Adrian Pelin ◽  
Jiahu Wang ◽  
John Bell ◽  
Fabrice Le Boeuf
Keyword(s):  
Oncolytic Viruses ◽  
In Vivo Distribution

scholarly journals Continuous Delivery of Stromal Cell-Derived Factor-1 from Alginate Scaffolds Accelerates Wound Healing

2010 ◽  
Vol 19 (4) ◽  
pp. 399-408 ◽  
Author(s):  
Sina Y. Rabbany ◽  
Joseph Pastore ◽  
Masaya Yamamoto ◽  
Tim Miller ◽  
Shahin Rafii ◽  
...  
Keyword(s):  
Wound Healing ◽  
Stromal Cell ◽  
Wound Closure ◽  
Tissue Injury ◽  
Unmet Need ◽  
Novel Therapy ◽  
Yorkshire Pigs ◽  
Stromal Cell Derived Factor

Proper wound diagnosis and management is an increasingly important clinical challenge and is a large and growing unmet need. Pressure ulcers, hard-to-heal wounds, and problematic surgical incisions are emerging at increasing frequencies. At present, the wound-healing industry is experiencing a paradigm shift towards innovative treatments that exploit nanotechnology, biomaterials, and biologics. Our study utilized an alginate hydrogel patch to deliver stromal cell-derived factor-1 (SDF-1), a naturally occurring chemokine that is rapidly overexpressed in response to tissue injury, to assess the potential effects SDF-1 therapy on wound closure rates and scar formation. Alginate patches were loaded with either purified recombinant human SDF-1 protein or plasmid expressing SDF-1 and the kinetics of SDF-1 release were measured both in vitro and in vivo in mice. Our studies demonstrate that although SDF-1 plasmid- and protein-loaded patches were able to release therapeutic product over hours to days, SDF-1 protein was released faster (in vivo Kd 0.55 days) than SDF-1 plasmid (in vivo Kd 3.67 days). We hypothesized that chronic SDF-1 delivery would be more effective in accelerating the rate of dermal wound closure in Yorkshire pigs with acute surgical wounds, a model that closely mimics human wound healing. Wounds treated with SDF-1 protein ( n = 10) and plasmid ( n = 6) loaded patches healed faster than sham ( n = 4) or control ( n = 4). At day 9, SDF-1-treated wounds significantly accelerated wound closure (55.0 ± 14.3% healed) compared to nontreated controls (8.2 ± 6.0%, p < 0.05). Furthermore, 38% of SDF-1-treated wounds were fully healed at day 9 (vs. none in controls) with very little evidence of scarring. These data suggest that patch-mediated SDF-1 delivery may ultimately provide a novel therapy for accelerating healing and reducing scarring in clinical wounds.

scholarly journals Retrospective Study on Personal Protective Equipment During Pandemic Link to Outbreak of Carbpenem-Resistant Enterobacteriace

2021 ◽  
Vol 1 (S1) ◽  
pp. s9-s10
Author(s):  
Kenisha Evans ◽  
Jennifer LeRose ◽  
Angela Beatriz Cruz ◽  
Lavina Jabbo ◽  
Teena Chopra
Keyword(s):  
Retrospective Study ◽  
Infection Control ◽  
Personal Protective Equipment ◽  
Horizontal Transmission ◽  
Control Measures ◽  
Protective Equipment ◽  
Local Health ◽  
Infection Rates ◽  
Infection Control Measures ◽  
The Impact

Background: In 2019, according to the Centers for Disease Control and Prevention, carbapenem-resistant Enterobacteriaceae (CRE), had cost the lives of >35,000 patients, particularly the most virulent plasmid-mediated New Delhi metallo-β-lactamase (NDM). Although healthcare systems normally have strict surveillance and infection control measures for CRE, the rapid emergence of novel SAR-CoV-2 and COVID-19 led to a shortage of personal protective equipment (PPE) and medical supplies. As a result, routine infection practices, such as contact precautions, were violated. Studies have shown this depletion and shift in resources compromised the control of infections such CRE leading to rising horizontal transmission. Method: A retrospective study was conducted at a tertiary healthcare system in Detroit, Michigan, to determine the impact of PPE shortages during the COVID-19 pandemic on NDM infection rates. The following periods were established during 2020 based on PPE availability: (1) pre-PPE shortage (January–June), (2) PPE shortage (July–October), and (3) post-PPE shortage (November–December). Rates of NDM per 10,000 patient days were compared between periods using the Wilcoxon signed rank-sum test. Isolates were confirmed resistant by NDM by molecular typing performed by the Michigan State Health Department. Patient characteristics were gathered by medical chart review and patient interviews by telephone. Results: Overall, the average rate of NDM infections was 1.82 ±1.5 per 10,000 patient days. Rates during the PPE shortage were significantly higher, averaging 3.6 ±1.1 cases per 10,000 patient days (P = .02). During this time, several infections occurred within patients on the same unit and/or patients with same treating team, suggesting possible horizontal transmission. Once PPE stock was replenished and isolation practices were reinstated, NDM infection rates decreased to 0.77 ±1.1 per 10,000 patient days. Conclusion: Control of CRE requires strategic planning with active surveillance, antimicrobial constructs, and infection control measures. The study illustrates that in times of crisis, such as the COVID-19 pandemic, the burden of effective infection control requires much more multidisciplinary efforts to prevent unintentional lapses in patient safety. A swift response by the state and local health departments at a tertiary-care healthcare center conveyed a positive mitigation of the highest clinical threats and decreased horizontal transmission of disease.Funding: NoDisclosures: None

scholarly journals Olaparib and Enzalutamide synergistically suppress HCC progression via the AR-mediated miR-146a-5p/BRCA1 signaling

2019 ◽  
Author(s):  
Jie Zhao ◽  
Yin Sun ◽  
Hui Lin ◽  
Fuju Chou ◽  
Yao Xiao ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Parp Inhibitor ◽  
Preclinical Study ◽  
Brca1 Expression ◽  
Novel Therapy ◽  
Damage Response ◽  
Synergistic Mechanism ◽  
Direct Binding

AbstractHepatocellular carcinoma (HCC) is one of most common malignant tumors worldwide, however, the treatment for advanced HCC remains unsatisfactory. Here we found that Olaparib, a FDA approved PARP inhibitor, could enhance the cytotoxicity in HCC cells with a lower BRCA1 expression, and suppressing the AR with either Enz or AR-shRNA could further increase the Olaparib sensitivity to better suppress the HCC cell growth via a synergistic mechanism that may involve suppressing the expression of BRCA1 and other DNA damage response (DDR) genes. Mechanism studies revealed that Enz/AR signaling might transcriptional regulting the miR-146a-5p expression via binding to the AREs on its 5’ promoter region, which could then lead to suppress the homologous recombination-related BRCA1 expression via direct binding to its 3’ UTR of mRNA. Preclinical study using an in vivo mouse model also proved that combined Enz plus Olaparib led to better suppression of the HCC progression. Together, these in vitro/in vivo data suggest that combining Enz and Olaparib may help in the development of a novel therapy to better suppress the HCC progression.

scholarly journals Efficient Killing of Multidrug-Resistant Intracellular Bacteria by AIEgens in Vivo

2020 ◽  
Author(s):  
Ying Li ◽  
Fei Liu ◽  
Jiangjiang Zhang ◽  
Xiaoye Liu ◽  
Peihong Xiao ◽  
...  
Keyword(s):  
Membrane Damage ◽  
Multidrug Resistant ◽  
Host Cells ◽  
Comparable Efficacy ◽  
Intracellular Bacteria ◽  
New Agents ◽  
Immune Clearance ◽  
Infected Cells ◽  
Dose Levels

<p><a>Bacteria infected cells acting as “Trojan horses” not only protect bacteria from antibiotic therapies and immune clearance, but also increase the dissemination of pathogens from the initial sites of infection. Antibiotics are hard and insufficient to treat such hidden intracellular bacteria, especially the multidrug</a>-resistant (MDR) bacteria. Herein, aggregation-induced emission luminogens (AIEgens) such as TBPs showed potent broad-spectrum bactericidal activity against both <a></a><a>extracellular and intracellular</a> Gram-positive pathogens at low-dose levels. TBPs triggered reactive oxygen species (ROS)-mediated membrane damage to kill bacteria, regardless of light irradiation. Additionally, such AIEgens activated mitochondria dependent autophagy to eliminate intracellular bacteria in host cells. Compared to the routinely used vancomycin in clinics, TBPs showed comparable efficacy against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) <i>in vivo</i>. Our studies demonstrate that AIEgens are promising new agents for the treatment of MDR bacteria associated infections.</p>

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