Download or read book Optimized Gene Engineering and Combination Therapies to Boost T Cell Immunotherapeutic Performance written by Jonathan Fisher and published by Frontiers Media SA. This book was released on 2024-04-25 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book T Cell Mediated Combination Immunotherapy written by Cary Francis Opel and published by . This book was released on 2016 with total page 139 pages. Available in PDF, EPUB and Kindle. Book excerpt: Immunotherapy is a broad treatment strategy that harnesses the immune system to fight off a particular condition or disease. Cancer immunotherapy is the specific application of agents designed to interact or stimulate the immune system to fight off tumors. Treatments as diverse as passive antibody therapy, cytokine support, and comprehensive adoptive T cell transfer make up the broad field of immunotherapeutics. Due to the naturally complex interactions inherent in the immune system, there are many options for therapeutic intervention, however, this same complexity makes it extremely difficult to optimize treatment strategies. Because of this, research into developing new immunotherapies, optimizing existing immunotherapies, and designing new combinations of immunotherapies is still critical in the fight against cancer. Although there have been ongoing successes of individual immunotherapies in the clinic, the complexity and interdependence of the immune system suggests that any single therapeutic intervention will be insufficient to reject established malignancies. Increased interest in applying combinations of immunotherapies in the clinic requires more thorough preclinical work to guide the designs of these studies. The work presented in this thesis focuses on developing combinations of immunotherapies to treat preclinical models of cancer, as well as studying the underlying mechanism of tumor control. T cells are potent mediators of cytotoxicity and when properly used in adoptive cell transfer (ACT) protocols, can be highly effective in the treatment of cancer. ACT consists of three steps: 1) harvesting and purifying T cells from the patient, 2) enriching or modifying the T cells to become tumor specific, and 3) reinfusing the T cells along with supporting therapies. Therapies given alongside ACT are often adjuvants designed to enhance T cell response. However, focusing therapies only on enhancing the activity of the transferred T cells may miss out on synergistic effects when other parts of the immune system are simultaneously engaged. To study the effect of adjuvant therapy on ACT, a preclinical murine model was analyzed. Large, established B16F10 tumors were controlled when pmel-1 T cells were given with a course of supportive MSA-IL2 cytokine therapy, however, no cures were observed. When a course of TA99 antibody therapy was added alongside ACT, a high rate of cures was observed. Flow cytometry of both circulating and tumor infiltrating pmel-1 cells showed massive expansion and activation. Additionally, tumor infiltration of neutrophils, NK cells, and DCs were greatly enhanced by adjuvant therapy. DCs in the tumor draining lymph nodes were largely unchanged by the therapies. Engagement of the humoral immune response was also observed in both treatment cases. Surprisingly, antibody therapy did not substantially alter any of the mechanistic observations made in this study, despite its critical role in achieving cures of tumors. While ACT is a highly effective therapy, its clinical applicability is hindered by the complexity of performing T cell transplants and manipulations. A more optimal solution would involve purely injectable treatments that could elicit the same level of tumor specific T cell response in conjunction with potent recruitment of the adaptive immune system against tumors. To achieve this, working in collaboration with the Irvine Lab, combinations of immunotherapy using up to four different components were tested to identify critical factors in the successful rejection of established tumors in preclinical models. The four components of tumor targeting antibody, cytokine support, checkpoint blockade, and cancer vaccine acted synergistically to reject tumors from B16F10, TC-1, and DD-Her2/neu cell lines. The cancer vaccine elicited large numbers of tumor-specific T cells, and acted as a replacement for ACT. By analyzing subset combinations of this full treatment, the roles of each therapeutic component were identified. CD8 T cells and cross-presenting DCs were critical to curing subcutaneous tumors. Cytokine therapy was indispensable for effective tumor control, promoted immune cell infiltration into the tumor, and led to an increase in DCs. In combination with the other therapies, vaccination against a tumor antigen elicited a strong immunological memory response that was able to reject subsequent tumor rechallenge, as well as promote antigen spreading to new epitopes. Successful combinations were demonstrated to be dependent on the recruitment of both the adaptive and innate branches of the immune system. Finally, the efficacy of this combination of treatments was demonstrated by controlling the growth of induced tumors in a BRaf/Pten model. Combination immunotherapy promises a future where synergistic treatments are specifically tailored to individual cancers leading to highly effective responses. However, determining the optimal combination of therapies, the complexity of dosing strategies, and the availability of targeted treatments are all barriers that must be overcome. The analysis presented here will make a significant contribution to the body of knowledge on immunotherapy as it has shown the importance of combining orthogonal immunotherapies in order to get durable cures to established tumors. These results will hopefully encourage combinations of orthogonally acting therapies based on T cells to achieve stronger clinical responses. By determining the necessary requirements for a strong, synergistic response to tumorous growths, more effective combination immunotherapy protocols may be designed in the future.

Download or read book Chimeric Antigen Receptor T Cell Therapies for Cancer E Book written by Daniel W. Lee and published by Elsevier Health Sciences. This book was released on 2019-11-30 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt: From patient referral to post-therapy management, Chimeric Antigen Receptor (CAR) T-Cell Therapies for Cancer: A Practical Guide presents a comprehensive view of CAR modified T-cells in a concise and practical format. Providing authoritative guidance on the implementation and management of CAR T-cell therapy from Drs. Daniel W. Lee and Nirali N. Shah, this clinical resource keeps you up to date on the latest developments in this rapidly evolving area. - Covers all clinical aspects, including patient referral, toxicities management, comorbidities, bridging therapy, post-CAR monitoring, and multidisciplinary approaches to supportive care. - Includes key topics on associated toxicities such as predictive biomarkers, infections, and multidisciplinary approaches to supportive care. - Presents current knowledge on FDA approved CAR T-cell products as well as developments on the horizon. - Editors and authors represent leading investigators in academia and worldwide pioneers of CAR therapy.

Download or read book Developments in T Cell Based Cancer Immunotherapies written by Paolo A. Ascierto and published by Humana. This book was released on 2019-03-14 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume illustrates the salient aspects of cancer biology relevant to the successful implementation of immunotherapy. Topics include enhancement of antigen-specific immune responses by anti-cancer vaccines, modulation of the function of T cells within the tumor microenvironment, and the effects of genetic, epigenetic, developmental, and environmental determinants on T cell function. Other topics covered include the ex vivo expansion of T or other immune cells and their genetic modification or reprogramming to increase their ability to survive and expand when adoptively transferred back to the patients. Specific attention is devoted to the genetic manipulation of T cells through the introduction of re-directed T cell receptors, chimeric antibody receptors, and other genetic manipulation aimed at improving their effectiveness as anti-cancer agents. Furthermore, the revolutionary role of checkpoint inhibitors and their potential in combination with other immunotherapeutic approaches or with standard chemo and radiation therapy are extensively discussed.

Download or read book Encyclopedia of Biomedical Gerontology written by and published by Academic Press. This book was released on 2019-11-20 with total page 1656 pages. Available in PDF, EPUB and Kindle. Book excerpt: Encyclopedia of Biomedical Gerontology, Three Volume Set presents a wide range of topics, ranging from what happens in the body during aging, the reasons and mechanisms relating to those age-related changes, and their clinical, psychological and social modulators and determinants. The book covers the biological and medical aspects of gerontology within the general framework of the biological basis of assessing age, biological mechanisms of aging, age-related changes in biological systems, human age-related diseases, the biomedical practicality and impracticality of interventions, and finally, the ethics of intervention. Provides a ‘one-stop’ resource to information written by world-leading scholars in the field of biomedical gerontology Fills a critical gap of information in a field that has seen significant progress in the last 10 years

Download or read book Interaction of Immune and Cancer Cells written by Magdalena Klink and published by Springer Nature. This book was released on 2022-02-14 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: Now, it its second edition, this book summarizes the role of immune cells in tumor suppression and progression. It describes in detail why tumor cells can survive and spread in spite of the antitumor response of immune cells. Since immunotherapy is an attractive approach to cancer therapy, this book also provides information on the two main strategies: monoclonal antibodies and adaptive T cell immunotherapy, with a focus on recent human clinical trials. A newly added chapter also focuses on the role of Natural Killer cells in tumor progression. The book provides a state-of-the-art, comprehensive overview of immune cells in cancer and is an indispensable resource for researchers and practitioners working or lecturing in the field of cancer research and immunology.

Download or read book Immunopharmacogenomics written by Yusuke Nakamura and published by Springer. This book was released on 2015-09-18 with total page 162 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book proposes immunogenomics, or immunopharmacogenomics, as the next-generation big science to uncover the role that the immune system plays in the pathogenesis of many diseases, by summarizing the importance of the deep sequencing of T-cell and B-cell receptors. Immunogenomics/immunopharmacogenomics, a genetic characterization of the immune system made possible by next-generation sequencing (NGS), will be important for the further understanding of the pathogenesis of various disease conditions. Abnormal immune responses in the body lead to development of autoimmune diseases and food allergies. Rejection of recipient cells and tissues, as well as severe immune reactions to donor cells, is also the result of uncontrolled immune responses in the recipient body. There have been many reports indicating that activated immune responses caused by the interaction of drugs and HLA are present in drug-induced skin hypersensitivity and liver toxicity. The importance of the host immune responses has been recognized in cancer treatments, not only for immunotherapy but also for cytotoxic agents and molecular targeted drugs. Hence, characterization of the T-cell receptor and B-cell receptor repertoire by means of NGS deep sequencing will ultimately make possible the identification of the molecular mechanisms that underlie various diseases and drug responses. In addition, this approach may contribute to the identification of antigens associated with the onset or progression of autoimmune diseases as well as food allergies. Although the germline alterations and somatic mutations have been extensively analyzed, changes or alterations of the immune responses during the course of various disease conditions or during various treatments have not been analyzed. It is also clear that computational analyses to draw meaningful inferences of functional recognition receptors on the immune cells remain a huge challenge.

Download or read book Tumor Microenvironment written by Alexander Birbrair and published by Springer Nature. This book was released on 2020-06-25 with total page 213 pages. Available in PDF, EPUB and Kindle. Book excerpt: Revealing essential roles of the tumor microenvironment in cancer progression, this book provides a comprehensive overview of the latest research in the field. A variety of topics are covered, including metabolism in the tumor microenvironment, stellate cells and endothelial progenitors in the tumor microenvironment, as well as the effects of HIV, viral hepatitis, and inflammation in the tumor microenvironment, and more. Taken alongside its companion volumes, Tumor Microenvironment: State of the Science updates us on what we know about various aspects of the tumor microenvironment, as well as future directions. This book is essential reading for advanced cell biology and cancer biology students as well as researchers seeking an update on research in the tumor microenvironment.

Download or read book Ex Vivo Cell Therapy written by Klaus Schindhelm and published by Academic Press. This book was released on 1999 with total page 392 pages. Available in PDF, EPUB and Kindle. Book excerpt: R.E. Nordon and K. Schindhelm, Introduction. -- L. Robb, A.G. Elefanty, and C.G. Begley, Transcriptional Control of Hematopoieses. -- R. Starr and N.A. Nicola, Cell Signaling by Hemopoietic Growth Factor Receptors. -- P.J. Simmons, D.N. Haylock, and J.-P. Lévesque, Influence of Cytokines and Adhesion Molecules on Hematopoietic Stem Cell Development. -- P.A. Rowlings, Allogeneic Hematopoietic Stem Cell Transplantation. -- U. Hahn and L.B. To, Autologous Stem Cell Transplantation. -- M.R. Vowels, Cord Blood Stem Cell Transplantation. -- S.R. Riddell, E.H. Warren, D. Lewinsohn, C. Yee, and P.D. Greenberg, Reconstitution of Immunity by Adoptive Immunotherapy with T Cells. -- L.Q. Sun, M. Miller, and G. Symonds, Exogenous Gene Transfer into Lymphoid and Hematopoietic Progenitor Cells. -- C. Dowding, T. Leemhuis, A. Jakubowski, and C. Reading, Process Development for Ex Vivo Cell Therapy. -- R.E. Nordon and K. Schindhelm, Cell Separation. -- P.W. Zandstra, C.J. Eaves, and J.M. Piret, Environ ...

Download or read book Tertiary Lymphoid Organs TLOs Powerhouses of Disease Immunity written by Changjun Yin and published by Frontiers Media SA. This book was released on 2017-05-22 with total page 237 pages. Available in PDF, EPUB and Kindle. Book excerpt: The immune system employs TLOs to elicit highly localized and forceful responses to unresolvable peripheral tissue inflammation. Current data indicate that TLOs are protective but they may also lead to collateral tissue injury and serve as nesting places to generate autoreactive lymphocytes. A better comprehension of these powerhouses of disease immunity will likely facilitate development to unprecedented and specific therapies to fight chronic inflammatory diseases.

Download or read book Innovations for Next Generation Antibody Drug Conjugates written by Marc Damelin and published by Springer. This book was released on 2018-05-29 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: Antibody-drug conjugates (ADCs) stand at the verge of a transformation. Scores of clinical programs have yielded only a few regulatory approvals, but a wave of technological innovation now empowers us to overcome past technical challenges. This volume focuses on the next generation of ADCs and the innovations that will enable them. The book inspires the future by integrating the field’s history with novel strategies and cutting-edge technologies. While the book primarily addresses ADCs for solid tumors, the last chapter explores the emerging interest in using ADCs to treat other diseases. The therapeutic rationale of ADCs is strong: to direct small molecules to the desired site of action (and away from normal tissues) by conjugation to antibodies or other targeting moieties. However, the combination of small and large molecules imposes deep complexity to lead optimization, pharmacokinetics, toxicology, analytics and manufacturing. The field has made significant advances in all of these areas by improving target selection, ADC design, manufacturing methods and clinical strategies. These innovations will inspire and educate scientists who are designing next-generation ADCs with the potential to transform the lives of patients.

Download or read book Bioreactor Systems for Tissue Engineering written by Cornelia Kasper and published by Springer Science & Business Media. This book was released on 2009-02-03 with total page 274 pages. Available in PDF, EPUB and Kindle. Book excerpt: The editors of this special volume would first like to thank all authors for their excellent contributions. We would also like to thank Prof. Dr. Thomas Scheper, Dr. Marion Hertel and Ulrike Kreusel for providing the opportunity to compose this volume and Springer for organizational and technical support. Tissue engineering represents one of the major emerging fields in modern b- technology; it combines different subjects ranging from biological and material sciences to engineering and clinical disciplines. The aim of tissue engineering is the development of therapeutic approaches to substitute diseased organs or tissues or improve their function. Therefore, three dimensional biocompatible materials are seeded with cells and cultivated in suitable systems to generate functional tissues. Many different aspects play a role in the formation of 3D tissue structures. In the first place the source of the used cells is of the utmost importance. To prevent tissue rejection or immune response, preferentially autologous cells are now used. In particular, stem cells from different sources are gaining exceptional importance as they can be differentiated into different tissues by using special media and supplements. In the field of biomaterials, numerous scaffold materials already exist but new composites are also being developed based on polymeric, natural or xenogenic sources. Moreover, a very important issue in tissue en- neering is the formation of tissues under well defined, controlled and reprod- ible conditions. Therefore, a substantial number of new bioreactors have been developed.

Download or read book Recombinant Poxviruses written by Matthew M. Binns and published by CRC Press. This book was released on 1992-05-27 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recombinant Poxviruses provides a comprehensive examination of poxviruses with an emphasis on the potential of these viruses as new vaccines. The book considers a wide range of issues involved in producing new genetically engineered live vaccines, such as efficacy, safety, stability, cost, host range, immune response, immunization route, use of multivalent vaccines, and need for revaccination. The opening chapter describes the origin of vaccinia virus, its use to eradicate smallpox, and the pathogenesis of poxvirus infections. Subsequent chapters examine the molecular biology of poxviruses, methods of constructing vaccinia virus recombinants, and applications; the use and immune responses induced by poxvirus recombinants as live vaccines; and the important issues of the safety and immunogenicity of vaccinia virus. The book's final two chapters report the progress that has been made developing avipoxviruses and parapoxviruses as candidate recombinant vaccines. Recombinant Poxviruses will be a welcome addition to the bookshelves of virologists, microbiologists, infectious disease specialists, and veterinarians.

Download or read book Advances in Precision Medicine Oncology written by Hilal Arnouk and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent advances in precision medicine and immuno-oncology have led to highly specific and efficacious cancer therapies such as monoclonal antibodies and immune checkpoint inhibitors (ICIs). This book provides an up-to-date overview of advances in the field of immuno-oncology. Chapters cover such topics as ICIs and how they mount a robust immune response against cancer cells as well as the response of ICIs to treatment predictive biomarkers and their potential immune-related adverse events (irAEs). Additionally, the book includes a comprehensive review of the powerful FDA-approved therapeutic agent doxorubicin, highlighting the molecular mechanisms behind doxorubicin's drug resistance and critical side effects.

Download or read book Immunotherapy written by Aung Naing and published by Springer Nature. This book was released on 2022-01-01 with total page 445 pages. Available in PDF, EPUB and Kindle. Book excerpt: The field of immuno-oncology continues to rapidly evolve as new insights to fight and treat cancer emerge. The fourth edition of Immunotherapy provides the most current overview of immuno-oncology in different cancer types and toxicities associated with immunotherapy. While immunotherapy has revolutionized the treatment landscape of several solid malignancies, several challenges still exist. Only a subset of patients derive clinical benefits; some do not respond at all, and others respond initially, only for their disease to progress later. Because these drugs can activate a broad range of immune cells, patients suffer from a unique set of side effects known as immune-related adverse events. As more immunotherapeutic agents are used in the clinic, it is important to provide updates about current and ongoing developments in the field to further research efforts and inform treatment decisions. The fourth edition will have a new focus on strategies to overcome the challenges associated with immunotherapy. Chapters will discuss topics such as biomarkers of response, resistance mechanisms, role of imaging in predicting immune-related adverse events, and management of immune-related adverse events. Written by leading experts conducting cutting-edge research, readers will gain up-to-date knowledge on the current state and future of immunotherapy.

Download or read book Heparanase written by Israel Vlodavsky and published by Springer Nature. This book was released on 2020-04-09 with total page 871 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by internationally recognized leaders in Heparanase biology, the book’s eight chapters offer an opportunity for scientists, clinicians and advanced students in cell biology, tumor biology and oncology to obtain a comprehensive understanding of Heparanase’s multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications. Proteases and their involvement in cancer progression have been well addressed and documented; however, the emerging premise presented within this book is that Heparanase is a master regulator of aggressive cancer phenotypes and crosstalk with the tumor microenvironment. This endoglycosidase contributes to tumor-mediated remodeling of the extracellular matrix and cell surfaces, augmenting the bioavailability of pro-tumorigenic and pro-inflammatory growth factors and cytokines that are bound to Heparan sulfate. Compelling evidence ties Heparanase with all steps of tumor progression including tumor initiation, growth, angiogenesis, metastasis, and chemoresistance, supporting the notion that Heparanase is an important contributor to the poor outcome of cancer patients and a validated target for therapy. Unlike Heparanase, heparanase-2, a close homolog of Heparanase, lacks enzymatic activity, inhibits Heparanase, and regulates selected genes that promote normal differentiation and tumor suppression. Written by internationally recognized leaders in Heparanase biology, this volume presents a comprehensive understanding of Heparanase’s multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications to scientists, clinicians and advanced students in cell biology, tumor biology and oncology.

Download or read book Oncoimmunology written by Laurence Zitvogel and published by Springer. This book was released on 2017-12-13 with total page 700 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.