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 Developments in T Cell Based Cancer Immunotherapies written by Paolo A. Ascierto and published by Humana Press. This book was released on 2015-11-26 with total page 315 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 NK Cells in Cancer Immunotherapy Successes and Challenges written by Anahid Jewett and published by Academic Press. This book was released on 2022-12-06 with total page 496 pages. Available in PDF, EPUB and Kindle. Book excerpt: NK Cells in Cancer Immunotherapy: Successes and Challenges explains the latest immunotherapeutic strategies, focusing on NK cells to allow the best and precise combination treatments to cancer patients. The book provides existing background knowledge in the field of immunotherapy and discusses future areas of research required to carry out cutting-edge, validated therapies. Chapters cover advances in immunotherapeutic strategies, in particular, the use of NK cells with and without T-cell therapy in the treatment of cancer. The book is a valuable resource for cancer researchers, oncologists, graduate students and those interested in learning more about novel strategies to treat cancer patients. Immunotherapy is fast becoming the method of choice for cancer therapy. Although remarkable advances have been made in the field of immunotherapy, there are significant challenges and difficulties ahead since many of the current immunotherapeutic strategies do not provide long-lasting treatment strategies, and therefore are not very effective. - Covers CAR/T and CAR/NK and adoptive NK cell therapy with and without T cell therapies - Discusses basic biology of NK cells and mouse models of human cancers and the role of NK cells in metastatic cancer and in cancer stem cells - Encompasses information on combination therapies using check point inhibition, adoptive transfer of cytotoxic effector cells, chemotherapeutic drugs and activating and inhibitory antibodies

Download or read book Synergistic Anti tumor Immune Response to Combination Immunotherapy Consisting of Anti tumor Antibodies Extended Half life Interleukin 2 and Other Immunomodulatory Agents written by Eric Franklin Zhu and published by . This book was released on 2016 with total page 123 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer immunotherapies under development have generally focused on either stimulating T-cell immunity or driving antibody-directed effector functions of the innate immune system such as antibody-dependent cell-mediated cytotoxicity (ADCC). However, as our understanding of antitumor immune responses grows, it has become increasingly apparent that single agent therapies may be insufficient to effectively stimulate all aspects of a complex robust anti-tumor response in a large proportion of patients. Thus, rational combination of single agent immunotherapies has become an area of increasing interest. In this work, we find that a combination of an anti-tumor antigen antibody and an untargeted IL-2 fusion protein with delayed systemic clearance induces significant tumor control in aggressive isogenic tumor models via a concerted innate and adaptive response. We find that this therapy induces the infiltration of various immune effectors such as neutrophils, eosinophils NK cells, and CD8+ T-cells that appear to direct cytolytic activity against tumor cells. This combination therapy also induces an intratumoral "cytokine storm," potentially re-polarizing the tumor microenvironment into one that is immunologically anti-tumor. We also identify cross-talk between NK cells and macrophages to induce intratumoral recruitment of neutrophils but with the requisite presence of anti-tumor antibodies and IL-2 simultaneously. We further enhanced the efficacy of this two-component therapy with the addition of a potent amphiphile-based anti-tumor peptide vaccine in combination with checkpoint blockade of anti-PD-I and anti-CTLA-4. This multi-component therapy was tested in a setting of a low-mutational burden GEM lung cancer model with a single known and targetable antigen: human carcinoembryonic antigen (CEA). We find that in the subcutaneous setting and autochthonous setting, both components of checkpoint blockade are necessary for full efficacy. While a 5- component therapy is admittedly unwieldy for clinical translation, understanding the complementary yet non-overlapping contributions of each agent may inform improved development of additional immunotherapy agents and their combinations in the clinic.

Download or read book Characterization of Anti tumor T Cell Specificities to Inform Engineering of Antigen targeted Immunotherapies written by Elizabeth E. Grace and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the past several decades, advances in immunotherapy have revolutionized cancer treatment. Immune checkpoint blockade has resulted in durable responses for some patients, but others have not seen the same benefits. T cells are essential to the success of many immunotherapies, as their receptors can recognize peptide antigens presented by major histocompatibility complexes (MHCs); productive recognition of antigens displayed by tumors results in T cell-mediated killing of the tumor cells. However, it is not always known what antigens are being recognized by cytotoxic T cells. Thus, there are many avenues of research being pursued to broaden and improve responses to cancer therapy, including T cell antigen identification and the development of combination immunotherapies.

Download or read book Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Cutaneous Melanoma written by and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Tumor Immunology and Immunotherapy written by Robert C. Rees and published by Oxford University Press, USA. This book was released on 2014 with total page 469 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tumor immunology and immunotherapy provides a comprehensive account of cancer immunity and immunotherapy. Examining recent results, current areas of interest and the specific issues that are affecting the research and development of vaccines, this book provides insight into how these problems may be overcome as viewed by leaders in the field.

Download or read book Guide to Immunotherapy written by Suzanne L. Walker and published by . This book was released on 2018-10 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Immunotherapy of Hepatocellular Carcinoma written by Tim F. Greten and published by Springer. This book was released on 2018-08-22 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this book we provide insights into liver – cancer and immunology. Experts in the field provide an overview over fundamental immunological questions in liver cancer and tumorimmunology, which form the base for immune based approaches in HCC, which gain increasing interest in the community due to first promising results obtained in early clinical trials. Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death in the United States. Treatment options are limited. Viral hepatitis is one of the major risk factors for HCC, which represents a typical “inflammation-induced” cancer. Immune-based treatment approaches have revolutionized oncology in recent years. Various treatment strategies have received FDA approval including dendritic cell vaccination, for prostate cancer as well as immune checkpoint inhibition targeting the CTLA4 or the PD1/PDL1 axis in melanoma, lung, and kidney cancer. Additionally, cell based therapies (adoptive T cell therapy, CAR T cells and TCR transduced T cells) have demonstrated significant efficacy in patients with B cell malignancies and melanoma. Immune checkpoint inhibitors in particular have generated enormous excitement across the entire field of oncology, providing a significant benefit to a minority of patients.

Download or read book Patient Derived Tumor Xenograft Models written by Rajesh Uthamanthil and published by Academic Press. This book was released on 2016-10-13 with total page 488 pages. Available in PDF, EPUB and Kindle. Book excerpt: Patient Derived Tumor Xenograft Models: Promise, Potential and Practice offers guidance on how to conduct PDX modeling and trials, including how to know when these models are appropriate for use, and how the data should be interpreted through the selection of immunodeficient strains. In addition, proper methodologies suitable for growing different type of tumors, acquisition of pathology, genomic and other data about the tumor, potential pitfalls, and confounding background pathologies that occur in these models are also included, as is a discussion of the facilities and infrastructure required to operate a PDX laboratory. - Offers guidance on data interpretation and regulatory aspects - Provides useful techniques and strategies for working with PDX models - Includes practical tools and potential pitfalls for best practices - Compiles all knowledge of PDX models research in one resource - Presents the results of first ever global survey on standards of PDX development and usage in academia and industry

Download or read book Critical Issues in Head and Neck Oncology written by Jan B. Vermorken and published by Springer Nature. This book was released on 2023-03-27 with total page 361 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is an open access book. With a wealth of exciting data emerging in this rapidly evolving field this book will review the state-of-the-art knowledge with emphasis on multidisciplinary decision and management of head and neck cancer. The book provides significant detail on a wide range of topics including: the role of new targets for treatment, immunotherapy, resistance mechanisms, standardizing molecular profiling programs, and new methods to guide therapeutic approaches. In addition different disease situations are addressed including different treatment approaches in primary disease and in recurrent and/or metastatic disease as well as new developments in pathology, surgery and reconstruction techniques, new systemic therapies in salivary gland cancer, and supportive care and follow-up. All disciplines involved in the treatment of head & neck cancer are covered with a focus on translation into daily practice. The 8th-THNO is designed for medical oncologists, head and neck surgeons, radiation oncologists, otolaryngologists, and other medical professionals involved in the treatment of patients with head and neck cancer.

Download or read book Hepatotoxicity written by Hyman J. Zimmerman and published by Lippincott Williams & Wilkins. This book was released on 1999 with total page 848 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by the foremost authority in the field, this volume is a comprehensive review of the multifaceted phenomenon of hepatotoxicity. Dr. Zimmerman examines the interface between chemicals and the liver; the latest research in experimental hepatotoxicology; the hepatotoxic risks of household, industrial, and environmental chemicals; and the adverse effects of drugs on the liver. This thoroughly revised, updated Second Edition features a greatly expanded section on the wide variety of drugs that can cause liver injury. For quick reference, an appendix lists these medications and their associated hepatic injuries. Also included are in-depth discussions of drug metabolism and factors affecting susceptibility to liver injury.

Download or read book Management of Hematologic Malignancies written by Susan O'Brien and published by Cambridge University Press. This book was released on 2010-11-18 with total page 526 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hematologic malignancies were the first human cancers to be studied in depth at the molecular level, and recent years have seen important advances in treatment. This comprehensive reference book covers the full range of hematologic malignancies, including all subtypes of leukemias, lymphomas, and plasma cell dyscrasias. Authored by internationally known experts, each chapter emphasizes diagnostic work-up, staging, and therapeutic approaches. Up-to-date hematopathology, treatment, and outcomes data are presented in a way which is directly applicable to patient care. Highly illustrated with color images, graphs, flowcharts and treatment algorithms, the book is perfect for quick clinical reference as well as providing detailed reference lists for further study. With its authoritative and practical focus and visually stimulating presentation, this is a key text for hematology and oncology fellows, physicians, oncology nurses, physician assistants and other healthcare workers in the field of oncology.

Download or read book Bispecific Antibodies for T Cell Based Immunotherapy written by Brian H. Santich and published by Frontiers Media SA. This book was released on 2021-01-21 with total page 97 pages. Available in PDF, EPUB and Kindle. Book excerpt: CK is affiliated with the Roche Innovation Center Zurich, holds stocks and has patents with Hoffmann-La Roche company. NKC reports receiving commercial research grants from Y-mabs Therapeutics and Abpro-Labs Inc.; holding ownership interest/equity/options in Y-Mabs Therapeutics Inc., and in Abpro-Labs, and owning stock options in Eureka Therapeutics. NKC is the inventor of pending and issued patents filed by MSK, including hu3F8 and 8H9 licensed to Ymabs Therapeutics, beta-glucan to Biotec Pharmacon, and HER2 bispecific antibody to Abpro-labs. NKC is an advisory board member for Abpro-Labs and Eureka Therapeutics

Download or read book Human IgG Fc Receptors written by Jan G. J. van de Winkel and published by . This book was released on 1996 with total page 266 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Antibody Fusion Proteins written by Steven M. Chamow and published by Wiley-Liss. This book was released on 1999-04-13 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: Thoroughly detailed and illustrated, this book examines the construction, properties, applications, and problems associated with specific types of fusion molecules used in clinical and research medicine. The editors present an overview of the field, followed by nine chapters divided into two general sections based on the two primary parts of the antibody molecule: Fab fusion proteins and Fc fusion proteins. In addition, numerous renowned scientists in the field have contributed outlines demonstrating man-made molecules that will be required not only to overcome the limitations of monoclonal antibodies, but also to extend the principle of selective targeting. Divided into specific, accessible sections, Antibody Fusion Proteins includes: * Chapters describing Fc fusion proteins, as well as several classes of antigen-binding proteins * Complete details on the design and molecular construction of genetically engineered fusion molecules * Useful information on molecular purification, large-scale production, practical applications, and their therapeutic potential * The latest data on forming fusion proteins with toxins, cytokines, or enzymes that can activate a prodrug