Harnessing Oncolytic Virus-mediated Antitumor Immunity


Book Description

Oncolytic viruses (OVs) have emerged as a promising anticancer treatment. OVs selectively infect, replicate in, and kill tumor cells. Oncolytic viral therapy occurs in two phases: an initial phase where the virus mediates direct oncolysis of tumor cells, and a second phase where an induced post-oncolytic immune response continues to mediate tumor destruction and retards progression of the disease. For a long time, the therapeutic efficacy was thought to depend mainly on the direct viral oncolysis based on their tumor selective replication and killing activities. But the post-oncolytic anti-tumor activity induced by the OV therapy is also a key factor for an efficient therapeutic activity. The topic adresses various strategies how to optimize OVs anti-tumor activity.




Cancer Immunology and Immunotherapy


Book Description

Delivery Technologies for Immuno-Oncology: Volume 1: Delivery Strategies and Engineering Technologies in Cancer Immunotherapy examines the challenges of delivering immuno-oncology therapies. Immuno-oncology (IO) is a growing field of medicine at the interface of immunology and cancer biology leading to development of novel therapeutic approaches, such as chimeric antigen receptor T-cell (CAR-T) and immune checkpoint blockade antibodies, that are clinically approved approaches for cancer therapy. Although currently approved IO approaches have shown tremendous promise for select types of cancers, broad application of IO strategies could even further improve the clinical success, especially for diseases such as pancreatic cancer, brain tumors where the success of IO so far has been limited. Nanotechnology-based targeted delivery strategies could improve the delivery efficiency of IO agents as well as provide additional avenues for novel therapeutic and vaccination strategies. Additionally, a number of locally-administered immunogenic scaffolds and therapeutic strategies, such as the use of STING agonist, could benefit from rationally designed biomaterials and delivery approaches. Delivery Technologies for Immuno-Oncology: Volume 1: Delivery Strategies and Engineering Technologies in Cancer Immunotherapy creates a comprehensive treaty that engages the scientific and medical community who are involved in the challenges of immunology, cancer biology, and therapeutics with possible solutions from the nanotechnology and drug delivery side. - Comprehensive treaty covering all aspects of immuno-oncology (IO) - Novel strategies for delivery of IO therapeutics and vaccines - Forecasting on the future of nanotechnology and drug delivery for IO




Epigenetic Modifications and Viral Infections


Book Description

Epigenetics is defined as the study of modifications of the genome, heritable during cell division that does not involve changes in DNA sequences. Up to date, epigenetic modifications involve at least three general mechanisms regulating gene expression: histone modifications, DNA methylation, and non-coding RNAs (ncRNAs). For the past two decades, an explosion in our interest and understanding of epigenetic mechanisms has been seen. This mainly based on the influence that epigenetic alterations have on an amazing number of biological processes, such as gene expression, imprinting, programmed DNA rearrangements, germ line silencing, developmentally cued stem cell division, and overall chromosomal stability and identity. It has become also evident that the constant exposure of living organisms to environment factors affects their genomes through epigenetic mechanisms. Viruses infecting animal cells are thought to play central roles in shaping the epigenetic scenario of infected cells. In this context it has become obvious that knowing the impact that viral infections have on the epigenetic control of their host cells will certainly lead to a better understanding of the interplay viruses have with animal cells. In fact, DNA viruses use host transcription factors as well as epigenetic regulators in such a way that they affect epigenetic control of gene expression that extends to host gene expression. At the same time, animal cells employ mechanisms controlling transcription factors and epigenetic processes, in order to eliminate viral infections. In summary, epigenetic mechanisms are involved in most virus-cell interactions. We now know that some viruses exhibit epigenetic immune evasion mechanisms to survive and propagate in their host; however, there is still much ambiguity over these epigenetic mechanisms of viral immune evasion, and most of the discovered mechanisms are still incomplete. Other animal viruses associated to cancer often deregulate cellular epigenetic mechanisms, silencing cellular tumor-suppressor genes and/or activating either viral or host cell oncogenes. In addition, in several cancers the down-regulation of tumor suppressor protein-coding genes and ncRNAs with growth inhibitory functions, such as miRNAs, have been closely linked to the presence of cell CpG island promoter hypermethylation. The goal of the aforementioned Research Topic is to bring together the key experimental and theoretical research, linking state-of-the-art knowledge about the epigenetic mechanisms involved in animal virus-cell interactions.




Overcoming Ovarian Cancer Chemoresistance


Book Description

Overcoming Ovarian Cancer Chemoresistance presents non-overlapping review chapters that discuss the state of the field in overcoming chemoresistance of ovarian cancer and treatment options before and following recurrence, considering the genetic makeup of the ovarian cancer patient and her tumor. With the uptake of both germline and somatic gene testing, clinicians can obtain a more comprehensive understanding of ovarian tumors and this book provides information to link the genetic makeup of a tumor (or patient) with the best available treatment. The book discusses topics such as strategies to fight chemo-resistance in ovarian cancer, circulating DNA as a monitor of response, BRCA mutations, ovarian cancer stem cells, immunotherapy and vaccines. Additionally, it brings a list of promising agents at clinical and pre-clinical stage that will impact the treatment in the near future. This book is a valuable source for cancer researchers, oncologists and several members of biomedical field who need to understand how to battle chemoresistance in ovarian cancer. - Provides a comprehensive view of both biological and genetic determinants of resistance, as well as technical approaches to monitor response - Discusses genetic reversions as a unique alteration and a new field of study - Includes a chapter on upcoming and promising agents that are in the pre-clinical and early clinical space, to set the stage for future directions in the field




Bugs as Drugs


Book Description

Examining the enormous potential of microbiome manipulation to improve health Associations between the composition of the intestinal microbiome and many human diseases, including inflammatory bowel disease, cardiovascular disease, metabolic disorders, and cancer, have been elegantly described in the past decade. Now, whole-genome sequencing, bioinformatics, and precision gene-editing techniques are being combined with centuries-old therapies, such as fecal microbiota transplantation, to translate current research into new diagnostics and therapeutics to treat complex diseases. Bugs as Drugs provides a much-needed overview of microbes in therapies and will serve as an excellent resource for scientists and clinicians as they carry out research and clinical studies on investigating the roles the microbiota plays in health and disease. In Bugs as Drugs, editors Robert A. Britton and Patrice D. Cani have assembled a fascinating collection of reviews that chart the history, current efforts, and future prospects of using microorganisms to fight disease and improve health. Sections cover traditional uses of probiotics, next-generation microbial therapeutics, controlling infectious diseases, and indirect strategies for manipulating the host microbiome. Topics presented include: How well-established probiotics support and improve host health by improving the composition of the intestinal microbiota of the host and by modulating the host immune response. The use of gene editing and recombinant DNA techniques to create tailored probiotics and to characterize next-generation beneficial microbes. For example, engineering that improves the anti-inflammatory profile of probiotics can reduce the number of colonic polyps formed, and lactobacilli can be transformed into targeted delivery systems carrying therapeutic proteins or bioengineered bacteriophage. The association of specific microbiota composition with colorectal cancer, liver diseases, osteoporosis, and inflammatory bowel disease. The gut microbiota has been proposed to serve as an organ involved in regulation of inflammation, immune function, and energy homeostasis. Fecal microbiota transplantation as a promising treatment for numerous diseases beyond C. difficile infection. Practical considerations for using fecal microbiota transplantation are provided, while it is acknowledged that more high-quality evidence is needed to ascertain the importance of strain specificity in positive treatment outcomes. Because systems biology approaches and synthetic engineering of microbes are now high-throughput and cost-effective, a much wider range of therapeutic possibilities can be explored and vetted. If you are looking for online access to the latest clinical microbiology content, please visit www.wiley.com/learn/clinmicronow.




Viral Nanoparticles


Book Description

This book overviews the applications of viral nanoparticles (VNPs) in areas ranging from materials science to biomedicine. It summarizes the many different VNP building blocks and describes chemistries that allow one to attach, entrap, or display functionalities on VNPs. The book outlines the strategies for the construction of 1-, 2-, and 3-D arrays, highlights the achievements in utilizing VNPs as tools for novel biosensors and nanoelectronic devices, and describes efforts in designing VNPs for biomedical applications, including their use as gene delivery vectors, novel vaccines, imaging modalities, and applications in targeted therapeutics.







Oncoimmunology


Book Description

In this book, leading experts in cancer immunotherapy join forces to provide a comprehensive guide that sets out the main principles of oncoimmunology and examines the latest advances and their implications for clinical practice, focusing in particular on drugs with FDA/EMA approvals and breakthrough status. The aim is to deliver a landmark educational tool that will serve as the definitive reference for MD and PhD students while also meeting the needs of established researchers and healthcare professionals. Immunotherapy-based approaches are now inducing long-lasting clinical responses across multiple histological types of neoplasia, in previously difficult-to-treat metastatic cancers. The future challenges for oncologists are to understand and exploit the cellular and molecular components of complex immune networks, to optimize combinatorial regimens, to avoid immune-related side effects, and to plan immunomonitoring studies for biomarker discovery. The editors hope that this book will guide future and established health professionals toward the effective application of cancer immunology and immunotherapy and contribute significantly to further progress in the field.




Cancer Cell Lines Part 1


Book Description

Continuous cell lines derived from human cancers are the most widely used resource in laboratory-based cancer research. The first 3 volumes of this series on Human Cell Culture are devoted to these cancer cell lines. The chapters in these first 3 volumes have a common aim. Their purpose is to address 3 questions of fundamental importance to the relevance of human cancer cell lines as model systems of each type of cancer: 1. Do the cell lines available accurately represent the clinical presentation? 2. Do the cell lines accurately represent the histopathology of the original tumors? 3. Do the cell lines accurately represent the molecular genetics of this type of cancer? The cancer cell lines available are derived, in most cases, from the more aggressive and advanced cancers. There are few cell lines derived from low grade organ-confined cancers. This gap can be filled with conditionally immortalized human cancer cell lines. We do not know why the success rate for establishing cell lines is so low for some types of cancer and so high for others. The histopathology of the tumor of origin and the extent to which the derived cell line retains the differentiated features of that tumor are critical. The concept that a single cell line derived from a tumor at a particular site is representative of tumors at that site is naïve and misleading.




Combinational Immunotherapy of Cancer: Novel Targets, Mechanisms, and Strategies


Book Description

Cancer immunotherapy, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) therapy, has revolutionized the paradigm in cancer treatment. However, the clinical outcome of immunotherapy varies considerably among patients and only a minority of patients achieve long-term clinical benefits. This is largely attributed to the fact that existing cancer immunotherapies, which concentrate on several classical targets (CTAL-4, PD-1/PD-L1, etc.) and limited types of immune cell populations (T cells), are insufficient to cope with the complexity of highly heterogeneous tumor microenvironment (TME). This calls for more efforts to not only expand our toolbox for manipulating anticancer immunity but also diversify our combinational strategies. To this end, it is urgent to deeper our understanding of cancer immunotherapy by using both experimental and computational methodologies from multi-scale perspectives: 1) novel targets from either tumor cells or non-tumor cells within TME (e.g., tumor intrinsic resistance drivers, new immune checkpoints, neoantigens), 2) in-depth characterization of more immune cell populations (e.g., macrophages, Tregs, B cells) and their interactions and dynamics within TME, 3) landscape of actionable targets in patient populations for combination design. These efforts will open the avenue of rational design of combinational immunotherapies, allowing researchers and clinicians to design novel targeting therapeutics or to optimally orchestrate combinatory strategies aiming to surmount resistance mechanisms and improve clinical outcomes.