scholarly journals Emerging Prospects for Nanoparticle-Enabled Cancer Immunotherapy

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Manal Ali Buabeid ◽  
El-Shaimaa A. Arafa ◽  
Ghulam Murtaza
Keyword(s):  
Cancer Treatment ◽  
Cancer Immunotherapy ◽  
Interventional Oncology ◽  
Review Article ◽  
Image Guided ◽  
Local Immunotherapy ◽  
Cancer Antigens ◽  
Tumor Environment ◽  
Limited Application ◽  
The Impact

One of the standards for cancer treatment is cancer immunotherapy which treats both primary and metastasized tumors. Although cancer immunotherapeutics show better outcomes as compared with conventional approaches of cancer treatment, the currently used cancer immunotherapeutics have limited application in delivering cancer antigens to immune cells. Conversely, in solid tumors, tumor microenvironment suppresses the immune system leading to the evasion of anticancer immunity. Some promising attempts have been made to overcome these drawbacks by using different approaches, for instance, the use of biomaterial-based nanoparticles. Accordingly, various studies involving the application of nanoparticles in cancer immunotherapy have been discussed in this review article. This review not only describes the modes of cancer immunotherapy to reveal the importance of nanoparticles in this modality but also narrates nanoparticle-mediated delivery of cancer antigens and therapeutic supplements. Moreover, the impact of nanoparticles on the immunosuppressive behavior of tumor environment has been discussed. The last part of this review deals with cancer immunotherapy using a combination of traditional interventional oncology approach and image-guided local immunotherapy against cancer. According to recent studies, cancer therapy can potentially be improved through nanoparticle-based immunotherapy. In addition, drawbacks associated with the currently used cancer immunotherapeutics can be fixed by using nanoparticles.

scholarly journals Antigen Selection for Enhanced Affinity T-Cell Receptor–Based Cancer Therapies

2016 ◽  
Vol 21 (8) ◽  
pp. 769-785 ◽  
Author(s):  
Emma S. Hickman ◽  
Martine E. Lomax ◽  
Bent K. Jakobsen
Keyword(s):  
T Cell ◽  
Cancer Immunotherapy ◽  
De Novo ◽  
Cell Receptor ◽  
T Cell Response ◽  
Adoptive Cell Transfer ◽  
Cytotoxic T Cell ◽  
Discovery Process ◽  
Cancer Antigens ◽  
The Impact

Evidence of adaptive immune responses in the prevention of cancer has been accumulating for decades. Spontaneous T-cell responses occur in multiple indications, bringing the study of de novo expressed cancer antigens to the fore and highlighting their potential as targets for cancer immunotherapy. Circumventing the immune-suppressive mechanisms that maintain tumor tolerance and driving an antitumor cytotoxic T-cell response in cancer patients may eradicate the tumor or block disease progression. Multiple strategies are being pursued to harness the cytotoxic potential of T cells clinically. Highly promising results are now emerging. The focus of this review is the target discovery process for cancer immune therapeutics based on affinity-matured T-cell receptors (TCRs). Target cancer antigens in the context of adoptive cell transfer technologies and soluble biologic agents are discussed. To appreciate the impact of TCR-based technology and understand the TCR discovery process, it is necessary to understand key differences between TCR-based therapy and other immunotherapy approaches. The review first summarizes key advances in the cancer immunotherapy field and then discusses the opportunities that TCR technology provides. The nature and breadth of molecular targets that are tractable to this approach are discussed, together with the challenges associated with finding them.

scholarly journals Musculoskeletal interventional oncology: current and future practices

2020 ◽  
Vol 93 (1115) ◽  
pp. 20200465 ◽  
Author(s):  
Roberto Luigi Cazzato ◽  
Julien Garnon ◽  
Guillaume Koch ◽  
Danoob Dalili ◽  
Pramod Prabhakar Rao ◽  
...  
Keyword(s):  
Clinical Management ◽  
Interventional Oncology ◽  
Rapid Evolution ◽  
Narrative Review ◽  
Image Guided ◽  
Indications For Treatment ◽  
Clinical Indications ◽  
Medical Oncologists ◽  
The Impact ◽  
Near Future

Management of musculoskeletal (MSK) tumours has traditionally been delivered by surgeons and medical oncologists. However, in recent years, image-guided interventional oncology (IO) has significantly impacted the clinical management of MSK tumours. With the rapid evolution of relevant technologies and the expanding range of clinical indications, it is likely that the impact of IO will significantly grow and further evolve in the near future. In this narrative review, we describe well-established and new interventional technologies that are currently integrating into the IO armamentarium available to radiologists to treat MSK tumours and illustrate new emerging IO indications for treatment.

Challenges and Issues in the Design of Micro-Machined Antennas - A Review

2020 ◽  
Vol 13 ◽  
Author(s):  
Ashish Kumar ◽  
Amar Partap Singh Pharwaha
Keyword(s):  
Patch Antenna ◽  
Ground Plane ◽  
Substrate Material ◽  
Review Article ◽  
High Index ◽  
Performance Characteristics ◽  
Machining Process ◽  
Patch Antennas ◽  
Micro Machining ◽  
The Impact

Background: Patch antennas are composed of the substrate material with patch and ground plane on the both sides of the substrate. The dimensions and performance characteristics of the antenna are highly influenced by the choice of the appropriate substrate depending upon the value of their dielectric constant. Generally, low index substrate materials are used to design the patch antenna but there are also some of the applications, which require the implementation of patch antenna design on high index substrate like silicon and gallium arsenide. Objective: The objective of this article is to review the design of antennas developed on high index substrate and the problems associated with the use of these materials as substrate. Also, main challenges and solutions have been discussed to improve the performance characteristics while using the high index substrates. Method: The review article has divided into various sections including the solution of the problems associated with the high index substrates in the form of micro-machining process. Along with this, types of micro machining and their applications have discussed in detail. Results: This review article investigates the various patch antennas designed with micro-machining technology and also discusses the impact of micro-machining process on the performance parameters of the patch antennas designed on high index substrates. Conclusion: By using the micro-machining process, the performance of patch antenna improves drastically but fabrication and tolerances at such minute structures is very tedious task for the antenna designers.

scholarly journals The impact of lymphedema on health-related quality of life up to 10 years after breast cancer treatment

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Mads G. Jørgensen ◽  
Navid M. Toyserkani ◽  
Frederik G. Hansen ◽  
Anette Bygum ◽  
Jens A. Sørensen
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Cancer Treatment ◽  
Breast Cancer Treatment ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related ◽  
The Impact

AbstractThe impact of breast cancer-related lymphedema (BCRL) on long-term quality of life is unknown. The aim of this study was to investigate the impact of BCRL on health-related quality of life (HRQoL) up to 10 years after breast cancer treatment. This regional population-based study enrolled patients treated for breast cancer with axillary lymph node dissection between January 1st 2007 and December 31th 2017. Follow up and assessments of the included patients were conducted between January 2019 and May 2020. The study outcome was HRQoL, evaluated with the Lymphedema Functioning, Disability and Health Questionnaire, the Disabilities of the Arm, Shoulder and Hand Questionnaire and the Short Form (36) Health Survey Questionnaire. Multivariate linear logistic regression models adjusted for confounders provided mean score differences (MDs) with 95% confidence intervals in each HRQoL scale and item. This study enrolled 244 patients with BCRL and 823 patients without BCRL. Patients with BCRL had significantly poorer HRQoL than patients without BCRL in 16 out of 18 HRQoL subscales, for example, in physical function (MDs 27, 95%CI: 24; 30), mental health (MDs 24, 95%CI: 21; 27) and social role functioning (MDs 20, 95%CI: 17; 23). Age, BMI, BCRL severity, hand and dominant arm affection had only minor impact on HRQoL (MDs < 5), suggesting a high degree of inter-individual variation in coping with lymphedema. This study showed that BCRL is associated with long-term impairments in HRQoL, especially affecting the physical and psychosocial domains. Surprisingly, BCRL diagnosis rather than clinical severity drove the largest impairments in HRQoL.

scholarly journals Radiopharmaceutical and Eu3+ doped gadolinium oxide nanoparticles mediated triple-excited fluorescence imaging and image-guided surgery

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaojing Shi ◽  
Caiguang Cao ◽  
Zeyu Zhang ◽  
Jie Tian ◽  
Zhenhua Hu
Keyword(s):  
Fluorescent Probes ◽  
Signal Intensity ◽  
Tumor Imaging ◽  
Tumor Resection ◽  
Optical Signal ◽  
Gadolinium Oxide ◽  
Image Guided Surgery ◽  
Guided Surgery ◽  
Image Guided ◽  
The Impact

AbstractCerenkov luminescence imaging (CLI) is a novel optical imaging technique that has been applied in clinic using various radionuclides and radiopharmaceuticals. However, clinical application of CLI has been limited by weak optical signal and restricted tissue penetration depth. Various fluorescent probes have been combined with radiopharmaceuticals for improved imaging performances. However, as most of these probes only interact with Cerenkov luminescence (CL), the low photon fluence of CL greatly restricted it’s interaction with fluorescent probes for in vivo imaging. Therefore, it is important to develop probes that can effectively convert energy beyond CL such as β and γ to the low energy optical signals. In this study, a Eu3+ doped gadolinium oxide (Gd2O3:Eu) was synthesized and combined with radiopharmaceuticals to achieve a red-shifted optical spectrum with less tissue scattering and enhanced optical signal intensity in this study. The interaction between Gd2O3:Eu and radiopharmaceutical were investigated using 18F-fluorodeoxyglucose (18F-FDG). The ex vivo optical signal intensity of the mixture of Gd2O3:Eu and 18F-FDG reached 369 times as high as that of CLI using 18F-FDG alone. To achieve improved biocompatibility, the Gd2O3:Eu nanoparticles were then modified with polyvinyl alcohol (PVA), and the resulted nanoprobe PVA modified Gd2O3:Eu (Gd2O3:Eu@PVA) was applied in intraoperative tumor imaging. Compared with 18F-FDG alone, intraoperative administration of Gd2O3:Eu@PVA and 18F-FDG combination achieved a much higher tumor-to-normal tissue ratio (TNR, 10.24 ± 2.24 vs. 1.87 ± 0.73, P = 0.0030). The use of Gd2O3:Eu@PVA and 18F-FDG also assisted intraoperative detection of tumors that were omitted by preoperative positron emission tomography (PET) imaging. Further experiment of image-guided surgery demonstrated feasibility of image-guided tumor resection using Gd2O3:Eu@PVA and 18F-FDG. In summary, Gd2O3:Eu can achieve significantly optimized imaging property when combined with 18F-FDG in intraoperative tumor imaging and image-guided tumor resection surgery. It is expected that the development of the Gd2O3:Eu nanoparticle will promote investigation and application of novel nanoparticles that can interact with radiopharmaceuticals for improved imaging properties. This work highlighted the impact of the nanoprobe that can be excited by radiopharmaceuticals emitting CL, β, and γ radiation for precisely imaging of tumor and intraoperatively guide tumor resection.

scholarly journals Alpha-Fetoprotein- and CD40Ligand-Expressing Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3375
Author(s):  
Annabelle Vogt ◽  
Farsaneh Sadeghlar ◽  
Tiyasha H. Ayub ◽  
Carlo Schneider ◽  
Christian Möhring ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Dendritic Cells ◽  
Tumor Regression ◽  
Combined Therapy ◽  
Term Survival ◽  
Effector Cells ◽  
Tumor Environment ◽  
The Impact

Dendritic cells (DC) as professional antigen presenting cells are able to prime T-cells against the tumor-associated antigen α-fetoprotein (AFP) for immunotherapy of hepatocellular carcinoma (HCC). However, a strong immunosuppressive tumor environment limits their efficacy in patients. The co-stimulation with CD40Ligand (CD40L) is critical in the maturation of DC and T-cell priming. In this study, the impact of intratumoral (i.t.) CD40L-expressing DC to improve vaccination with murine (m)AFP-transduced DC (Ad-mAFP-DC) was analyzed in subcutaneous (s.c.) and orthotopic murine HCC. Murine DC were adenovirally transduced with Ad-mAFP or Ad-CD40L. Hepa129-mAFP-cells were injected into the right flank or the liver of C3H-mice to induce subcutaneous (s.c.) and orthotopic HCC. For treatments, 106 Ad-mAFP-transduced DC were inoculated s.c. followed by 106 CD40L-expressing DC injected intratumorally (i.t.). S.c. inoculation with Ad-mAFP-transduced DC, as vaccine, induced a delay of tumor-growth of AFP-positive HCC compared to controls. When s.c.-inoculation of Ad-mAFP-DC was combined with i.t.-application of Ad-CD40L-DC synergistic antitumoral effects were observed and complete remissions and long-term survival in 62% of tumor-bearing animals were achieved. Analysis of the tumor environment at different time points revealed that s.c.-vaccination with Ad-mAFP-DC seems to stimulate tumor-specific effector cells, allowing an earlier recruitment of effector T-cells and a Th1 shift within the tumors. After i.t. co-stimulation with Ad-CD40L-DC, production of Th1-cytokines was strongly increased and accompanied by a robust tumor infiltration of mature DC, activated CD4+-, CD8+-T-cells as well as reduction of regulatory T-cells. Moreover, Ad-CD40L-DC induced tumor cell apoptosis. Intratumoral co-stimulation with CD40L-expressing DC significantly improves vaccination with Ad-mAFP-DC in pre-established HCC in vivo. Combined therapy caused an early and strong Th1-shift in the tumor environment as well as higher tumor apoptosis, leading to synergistic tumor regression of HCC. Thus, CD40L co-stimulation represents a promising tool for improving DC-based immunotherapy of HCC.

scholarly journals P9 A study to investigate the impact of the COVID-19 pandemic on paediatric cancer patients: an international, multicentre, observational cohort study (COVIDPaedsCancer)

BJS Open ◽  
2021 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
◽  
Soham Bandyopadhyay
Keyword(s):  
Cohort Study ◽  
Cancer Treatment ◽  
Childhood Cancer ◽  
Multivariate Logistic Regression Analysis ◽  
Global Health Research ◽  
Cancer Outcomes ◽  
Paediatric Cancer ◽  
Cancer Management ◽  
Anti Cancer ◽  
The Impact

Abstract Introduction Childhood cancers are a leading cause of non-communicable disease deaths for paediatric patients around the world. The COVID-19 pandemic may have impacted on global children’s cancer services, which can have consequences for childhood cancer outcomes. The Global Health Research Group on Children’s Non-Communicable Diseases (Global Children’s NCDs) is currently undertaking the first international study to determine the variation in paediatric cancer management during the COVID-19 pandemic, and the short to medium term impacts on childhood cancer outcomes. Methods and analysis This is a multicentre, international, cohort study that will use routinely collected hospital data in a de-identified and anonymised form. Patients will be recruited consecutively into the study, with a 12 -month follow-up period. Patients will be included if they are below the age of 18 years and undergoing anti-cancer treatment for the following cancers: Acute lymphoblastic leukaemia, Burkitt’s Lymphoma, Hodgkin's lymphoma, Wilms Tumour, Sarcoma, Retinoblastoma, Gliomas, Medulloblastomas and Neuroblastomas. Patients must be newly presented or be undergoing active anti-cancer treatment from the 12th March 2020 to the 12th December 2020. The primary objective of the study is to determine 30- and 90-day all-cause mortality rates. This study will examine the factors that influenced these outcomes. Chi-squared analysis will be used to compare mortality between low and middle-income countries and high-income countries. Multilevel, multivariate logistic regression analysis will be undertaken to identify patient-level and hospital-level factors affecting outcomes with adjustment for confounding factors. Ethics and dissemination At the host centre, this study was deemed to be exempt from ethical committee approval due to the use of anonymised registry data. At other centres, participating collaborators have gained local approvals in accordance with their institutional ethical regulations. Collaborators will be encouraged to present the results locally, nationally, and internationally. The results will be submitted for publication in a peer reviewed journal.

The impact of mitochondria on cancer treatment resistance

2021 ◽  
Author(s):  
Michelle van der Merwe ◽  
Gustav van Niekerk ◽  
Carla Fourie ◽  
Manisha du Plessis ◽  
Anna-Mart Engelbrecht
Keyword(s):  
Cancer Treatment ◽  
Treatment Resistance ◽  
The Impact

128 Development of an M1-polarized, non-viral chimeric antigen receptor macrophage (CAR-M) platform for cancer immunotherapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A141-A141
Author(s):  
Yumi Ohtani ◽  
Kayleigh Ross ◽  
Aditya Dandekar ◽  
Rashid Gabbasov ◽  
Michael Klichinsky
Keyword(s):  
Cancer Immunotherapy ◽  
Chimeric Antigen Receptor ◽  
Scale Up ◽  
Antigen Receptor ◽  
Innate Immune ◽  
List Type ◽  
M1 Phenotype ◽  
The Impact ◽  
Anti Tumor Activity ◽  
Immunosuppressive Factors

BackgroundWe have previously developed CAR-M as a novel cell therapy approach for the treatment of solid tumors.1 CAR-M have the potential to overcome key challenges that cell therapies face in the solid tumor setting – tumor infiltration, immunosuppression, lymphocyte exclusion – and can induce epitope spreading to overcome target antigen heterogeneity. While macrophages transduced with the adenoviral vector Ad5f35 (Ad CAR-M) traffic to tumors, provide robust anti-tumor activity, and recruit and activate T cells, we sought to identify a robust non-viral method of macrophage engineering in order to reduce the cost of goods, manufacturing complexity, and potential immunogenicity associated with viral vectors.MethodsAs innate immune cells, macrophages detect exogenous nucleic acids and respond with inflammatory and apoptotic programs. Thus, we sought to identify a means of mRNA delivery that avoids recognition by innate immune sensors. We screened a broad panel of mRNA encoding an anti-HER2 CAR comprising multiplexed 5’Cap and base modifications using an optimized and scalable electroporation approach and evaluated the impact of interferon-β priming on CAR-M phenotype and function.ResultsWe identified the optimal multiplexed mRNA modifications that led to maximal macrophage viability, transfection efficiency, intensity of CAR expression, and duration of expression. Non-viral HER2 CAR-M phagocytosed and killed human HER2+ tumor cells. Unlike Ad CAR-M, mRNA CAR-M were not skewed toward an M1 state by mRNA electroporation. Priming non-viral CAR-M with IFN-β induced a durable M1 phenotype, as shown by stable upregulation of numerous M1 markers and pathways. IFN-β priming significantly enhanced the anti-tumor activity of CAR but not control macrophages. IFN-β primed mRNA CAR-M were resistant to M2 conversion, maintaining an M1 phenotype despite challenge with various immunosuppressive factors, and converted bystander M2 macrophages toward M1. Interestingly, priming mRNA CAR-M with IFN-β significantly enhanced the persistence of CAR expression, overcoming the known issue of rapid mRNA turnover. RNA-seq analysis revealed that IFN-β priming affected pathways involved in increasing translation and decreasing RNA degradation in human macrophages.ConclusionsWe have established a novel, optimized non-viral CAR-M platform based on chemically modified mRNA and IFN-β priming. IFN-β priming induced a durable M1 phenotype, improved CAR expression, improved CAR persistence, led to enhanced anti-tumor function, and rendered resistance to immunosuppressive factors. This novel platform is amenable to scale-up, GMP manufacturing, and represents an advance in the development of CAR-M.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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