Ex Vivo Engineering of the Tumor Microenvironment

Ex Vivo Engineering of the Tumor Microenvironment PDF Author: Amir R. Aref
Publisher: Springer
ISBN: 3319453971
Category : Medical
Languages : en
Pages : 142

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Book Description
This volume will outline how to recreate the tumor microenvironment, to culture primary tumors without the need for developmental priming factors, and to deliver targeted therapeutics in a manner that recapitulates pharmacokinetics in vivo. Much of what may be learned from this volume will aid in understanding many aspects of the enhanced study of tumor cell biology in a physiologic context, open new avenues for drug screening and biomarker development, and accelerate the preclinical evaluation of novel personalized medicine strategies for patients in real time.

Ex Vivo Engineering of the Tumor Microenvironment

Ex Vivo Engineering of the Tumor Microenvironment PDF Author: Amir R. Aref
Publisher: Springer
ISBN: 3319453971
Category : Medical
Languages : en
Pages : 142

Get Book Here

Book Description
This volume will outline how to recreate the tumor microenvironment, to culture primary tumors without the need for developmental priming factors, and to deliver targeted therapeutics in a manner that recapitulates pharmacokinetics in vivo. Much of what may be learned from this volume will aid in understanding many aspects of the enhanced study of tumor cell biology in a physiologic context, open new avenues for drug screening and biomarker development, and accelerate the preclinical evaluation of novel personalized medicine strategies for patients in real time.

The Tumor Microenvironment

The Tumor Microenvironment PDF Author: Josie Ursini-Siegel
Publisher: Springer Nature
ISBN: 107162914X
Category : Medical
Languages : en
Pages : 417

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Book Description
This second edition provides update and new chapters detailing core and emerging in vitro and in vivo protocols. Chapters guide readers through cellular and molecular biology approaches, in vivo genetic approaches, various “omics”-based strategies, therapeutic strategies, and advanced techniques in the fields of tissue engineering and nanotechnology. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, The Tumor Microenvironment: Methods and Protocols, Second Edition is a valuable resource for both novice and expert scientists in this developing field.

Biomechanics in Oncology

Biomechanics in Oncology PDF Author: Cheng Dong
Publisher: Springer
ISBN: 3319952943
Category : Medical
Languages : en
Pages : 376

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Book Description
This book covers multi-scale biomechanics for oncology, ranging from cells and tissues to whole organ. Topics covered include, but not limited to, biomaterials in mechano-oncology, non-invasive imaging techniques, mechanical models of cell migration, cancer cell mechanics, and platelet-based drug delivery for cancer applications. This is an ideal book for graduate students, biomedical engineers, and researchers in the field of mechanobiology and oncology. This book also: Describes how mechanical properties of cancer cells, the extracellular matrix, tumor microenvironment and immuno-editing, and fluid flow dynamics contribute to tumor progression and the metastatic process Provides the latest research on non-invasive imaging, including traction force microscopy and brillouin confocal microscopy Includes insight into NCIs’ role in supporting biomechanics in oncology research Details how biomaterials in mechano-oncology can be used as a means to tune materials to study cancer

Engineering the Vascular Tumor Microenvironment

Engineering the Vascular Tumor Microenvironment PDF Author: Seema Mai Ehsan
Publisher:
ISBN: 9781321093780
Category :
Languages : en
Pages : 100

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Book Description
Cancer drug development remains a costly and inefficient endeavor that often translates to limited clinical success. While most therapies focus on stalling the growth of or eradicating tumor cells directly, the microenvironment in which these cells inhabit plays a hugely influential role in defining drug efficacy and disease progression. The supporting vasculature system as well as the interstitial extracellular matrix are particularly consequential to the transport, distribution, and uptake of therapeutics. While it is known that the host microenvironment may enable the advancement of malignancy and even the development of resistance, much of the mechanistic understanding by which this regulation occurs remains unclear. This is due in part to a lack of physiologically relevant models, though advancements in the emerging field of "tumor engineering" are beginning to challenge this. The transition away from incompatible animal models and simplified two-dimensional cultures has brought about the creation of advanced three-dimensional models in order to better simulate and test the microenvironmental characteristics that define human cancers. Nonetheless, few systems are able to capture the full range of authentic, complex in vivo events such as neovascularization, intravasation, and variable oxygen distribution. This work will explore the details of developing biologically-inspired, highly controlled in vitro tumor microenvironments to replicate and investigate these events. Such systems have the potential to mediate successful translation of preclinical research to clinical significance, while also providing mechanistic insight into the early stages of tumor progression and metastasis.

Tumor Organoids

Tumor Organoids PDF Author: Shay Soker
Publisher: Humana Press
ISBN: 3319605119
Category : Medical
Languages : en
Pages : 213

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Book Description
Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.

Engineering and Physical Approaches to Cancer

Engineering and Physical Approaches to Cancer PDF Author: Ian Y. Wong
Publisher: Springer Nature
ISBN: 3031228022
Category : Medical
Languages : en
Pages : 334

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Book Description
Engineering and Physical Approaches to Cancer addresses the newest research at this interface between cancer biology and the physical sciences. Several chapters address the mechanobiology of collective and individual cell migration, including experimental, theoretical, and computational perspectives. Other chapters consider the crosstalk of biological, chemical, and physical cues in the tumor microenvironment, including the role of senescence, polyploid giant cells, TGF-beta, metabolism, and immune cells. Further, chapters focus on circulating tumor cells and metastatic colonization, highlighting both bioengineered models as well as diagnostic technologies. Further, this book features the work of emerging and diverse investigators in this field, who have already made impressive cross-disciplinary scientific contributions. This book is designed for a general audience, particularly researchers conversant in cancer biology but less familiar with engineering (and vice-versa). Thus, we envision that this book will be suitable for faculty, postdoctoral fellows, and advanced graduate students across medicine, biological sciences, and engineering. We also anticipate this book will be of interest to medical professionals and trainees, as well as researchers in the pharmaceutical and biomedical device industry. Describes physical aspects of cancer, including collective cell migration, the aberrant tumor microenvironment, circulating tumor cells, and metastatic colonization. First volume available on the topic of physical aspects of cancer

Engineering Chimeric Antigen Receptors to Overcome the Immunosuppressive Solid Tumor Microenvironment

Engineering Chimeric Antigen Receptors to Overcome the Immunosuppressive Solid Tumor Microenvironment PDF Author: Andrew J Hou
Publisher:
ISBN:
Category :
Languages : en
Pages : 118

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Book Description
Adoptive T-cell therapy is a cancer treatment strategy where T cells from a cancer patient are harvested, modified ex vivo to target tumor cells, and subsequently reinfused back into the patient's body. Although remarkably successful against blood-based B-cell malignancies, efficacy has been limited against solid tumors, in large part due to the immunosuppressive tumor microenvironment (TME). Among the many inhibitory factors in the TME, transforming growth factor-beta (TGF-[Beta]) plays a prominent role in suppressing anti-tumor immunity through both direct inhibition of T-cell cytotoxicity, as well as recruitment and polarization of immunosuppressive cell types such as myeloid-derived suppressor cells and regulatory T cells. We therefore hypothesized that T-cell function in the solid TME could be potentiated by pairing tumor-targeting CARs with TGF-[Beta] CARs that program T-cell activation, rather than inhibition, in the presence of TGF-[Beta]. Wefirst verified that TGF-[Beta] CAR expression is neither counterproductive to cytotoxic T-cell function, nor does it pose a significant risk of toxicity. Pairing TGF-[Beta] CARs with tumor-specific TCRs or CARs did not significantly enhance therapeutic outcomes of adoptive T-cell transfer in preclinical models of melanoma and prostate cancer, warranting further engineering efforts. In models of glioblastoma, however, single-chain bispecific CAR-T cells targeting TGF-[Beta] and tumor antigen were not only more resistant to tumor-mediated dysfunction, but also remodeled the immune-cell composition of the tumor microenvironment to potentiate anti-tumor immunity.

An Implantable Device for Manipulation of the in Vivo Tumor Microenvironment

An Implantable Device for Manipulation of the in Vivo Tumor Microenvironment PDF Author: James K. Williams
Publisher:
ISBN:
Category : BioMEMS.
Languages : en
Pages : 117

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Book Description


An Ex Vivo 3D Tumor Microenvironment-Mimicry Culture to Study TAM Modulation

An Ex Vivo 3D Tumor Microenvironment-Mimicry Culture to Study TAM Modulation PDF Author: Lili Yang
Publisher: Eliva Press
ISBN: 9789994982899
Category :
Languages : en
Pages : 0

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Book Description
Tumor-associated macrophages (TAMs) accumulate in the solid tumor microenvironment (TME) and have been shown to promote tumor growth and dampen antitumor immune responses. TAM-mediated suppression of T-cell antitumor reactivity is considered to be a major obstacle for many immunotherapies, including immune checkpoint blockade and adoptive T/CAR-T-cell therapies. An ex vivo culture system closely mimicking the TME can greatly facilitate the study of cancer immunotherapies. Here, we report the development of a 3D TME-mimicry culture that is comprised of the three major components of a human TME, including human tumor cells, TAMs, and tumor antigen-specific T cells. This TME-mimicry culture can readout the TAM-mediated suppression of T-cell antitumor reactivity, and therefore can be used to study TAM modulation of T-cell-based cancer immunotherapy. As a proof-of-principle, the studies of a PD-1/PD-L1 blockade therapy and a MAO-A blockade therapy were performed and validated.

Tumor Engineering

Tumor Engineering PDF Author:
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Book Description
Advances in tissue engineering have been accomplished for years by employing biomimetic strategies to provide cells with aspects of their original microenvironment necessary to reconstitute a unit of both form and function for a given tissue. We believe that the most critical hallmark of cancer is loss of integration of architecture and function; thus, it stands to reason that similar strategies could be employed to understand tumor biology. In this commentary, we discuss work contributed by Fischbach-Teschl and colleagues to this special issue of Tissue Engineering in the context of 'tumor engineering', that is, the construction of complex cell culture models that recapitulate aspects of the in vivo tumor microenvironment to study the dynamics of tumor development, progression, and therapy on multiple scales. We provide examples of fundamental questions that could be answered by developing such models, and encourage the continued collaboration between physical scientists and life scientists not only for regenerative purposes, but also to unravel the complexity that is the tumor microenvironment. In 1993, Vacanti and Langer cast a spotlight on the growing gap between patients in need of organ transplants and the amount of available donor organs; they reaffirmed that tissue engineering could eventually address this problem by 'applying principles of engineering and the life sciences toward the development of biological substitutes. Mortality figures and direct health care costs for cancer patients rival those of patients who experience organ failure. Cancer is the second leading cause of death in the United States (Source: American Cancer Society) and it is estimated that direct medical costs for cancer patients approach $100B yearly in the United States alone (Source: National Cancer Institute). In addition, any promising therapy that emerges from the laboratory costs roughly $1.7B to take from bench to bedside. Whereas we have indeed waged war on cancer, the training grounds have largely consisted of small rodents, despite marked differences between human and mouse physiology, or plastic dishes, even though just like our tissues and organs most tumors exist within three-dimensional proteinacious milieus. One could argue that this is comparable to training for a desert war in the arctic. In this special issue of tissue engineering, Fischbach-Teschl and colleagues build a strong case for engineering complex cultures analogous to normal organs to tractably model aspects of the human tumor microenvironment that simply cannot be reproduced with traditional two-dimensional cell culture techniques and that cannot be studied in a controlled fashion in vivo. This idea has gained considerable traction of late as concepts presented and convincingly shown years ago have only now begun to be appreciated. Perhaps, then, it is time to organize those who wish to build complex tumor models to study cancer biology under a common umbrella. Accordingly, we propose that tumor engineering be defined as the construction of complex culture models that recapitulate aspects of the in vivo tumor microenvironment to study the dynamics of tumor development, progression, and therapy on multiple scales. Inherent in this definition is the collaboration that must occur between physical and life scientists to guide the design of patterning techniques, materials, and imaging modalities for the study of cancer from the subcellular to tissue level in physiologically relevant contexts. To date, the most successful tissue engineering approaches have employed methods that recapitulate the composition, architecture, and/or chemical presentation of native tissue. For instance, induction of blood vessel growth for therapeutic purposes has been achieved with sequential release of vascular endothelial growth factor (VEGF) and platelet derived growth factor to induce and stabilize blood vessels. This approach imitates that which occurs during physiological angiogenesis as a result of heterotypic interactions between endothelium and stroma. Employing such biomimetic strategies has already led to success in cancer research. Studying tumors in 3D has proven far more accurate in reproducing in vivo growth characteristics and chemotherapeutic resistance than 2D approaches. A number of animal studies and co-culture experiments have identified also the importance of interactions with other nonmalignant cell types - such as endothelial cells, fibroblasts, adipocytes, leukocytes, and circulating progenitors - to support and sustain tumor growth, invasion, and metastasis. Reproducing not only the 'dynamic reciprocity' but also the 'dynamic cooperativity' between these constituents in a spatially, temporally, and functionally accurate fashion presents quite a challenge for engineering tumors. So, why do it? The reason is to ask important fundamental questions that cannot easily be answered in vivo or on tissue culture plastic for the reasons mentioned.