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 Experimental and Applied Immunotherapy written by Jeffrey Medin and published by Springer Science & Business Media. This book was released on 2010-12-03 with total page 447 pages. Available in PDF, EPUB and Kindle. Book excerpt: Immunotherapy is now recognized as an essential component of treatment for a wide variety of cancers. It is an interdisciplinary field that is critically dependent upon an improved understanding of a vast network of cross-regulatory cellular populations and a diversity of molecular effectors; it is a leading example of translational medicine with a favorable concept-to-clinical-trial timeframe of just a few years. There are many established immunotherapies already in existence, but there are exciting new cancer immunotherapies just on the horizon, which are likely to be more potent, less toxic and more cost effective than many therapies currently in use. Experimental and Applied Immunotherapy is a state-of-the-art text offering a roadmap leading to the creation of these future cancer-fighting immunotherapies. It includes essays by leading researchers that cover a wide variety of topics including T cell and non-T cell therapy, monoclonal antibody therapy, dendritic cell-based cancer vaccines, mesenchymal stromal cells, negative regulators in cancer immunology and immunotherapy, non-cellular aspects of cancer immunotherapy, the combining of cancer vaccines with conventional therapies, the combining of oncolytic viruses with cancer immunotherapy, transplantation, and more. The field of immunotherapy holds great promise that will soon come to fruition if creative investigators can bridge seemingly disparate disciplines, such as T cell therapy, gene therapy, and transplantation therapy. This text is a vital tool in the building of that bridge.

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 Novel Strategies for Cancer Immunotherapy Targeting Immune Mediated Suppressive Mechanisms written by Virginie Lafont and published by Frontiers Media SA. This book was released on 2021-07-02 with total page 182 pages. Available in PDF, EPUB and Kindle. Book excerpt:

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 Analyzing T Cell Responses written by Dirk Nagorsen and published by Springer Science & Business Media. This book was released on 2006-01-16 with total page 313 pages. Available in PDF, EPUB and Kindle. Book excerpt: Active specific immunotherapy is a promising but investigational modality in the management of cancer patients. Currently, several different cancer vaccine formulations such as peptides, proteins, antigen-pulsed dendritic cells, whole tumor cells, etc. in combination with various adjuvants and carriers are being evaluated in clinical trials (1-3). To determine the optimal cancer vaccine strategy, a surrogate immunological end-point that correlates with clinical outcome needs to be defined, since it would facilitate the rapid comparison of these various formulations. Traditional immunological assays such as ELISA, proliferation and cytotoxicity assays can detect immune responses in vaccinated patients but are not quantitative. In contrast, novel assays such as enzyme-linked immunospot (ELISPOT) assay, intracellular cytokine assay and tetramer assay can quantitate the frequency of antigen-specific T cells. Of these, the ELISPOT assay has the 5 lowest detection limit with 1/10 peripheral blood mononuclear cells (PBMC) and has been determined to be one of the most useful assays to evaluate immune response to cancer vaccines (4). However, the IFN-? ELISPOT assay is not an exclusive measure of cytotoxic T-lymphocyte (CTL) activity as non-cytotoxic cells can also secrete IFN-?. Additionally, CTL with lytic activity do not always secrete IFN-? (5). A more relevant approach to assess functional activity of cytotoxic lymphocytes would be to measure the secretion of molecules that are associated with lytic activity. One of the major mechanisms of cell-mediated cytotoxicity involves exocytosis of cytoplasmic granules from the effector toward the target cell.

Download or read book Anti tumor Activity of Cytotoxic Immune Cells Basic Research and Clinical Perspectives written by Malgorzata Firczuk and published by Frontiers Media SA. This book was released on 2024-05-24 with total page 121 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are powerful effectors of antitumor immunity. CTL recognize tumor antigens presented by human leukocyte antigen (HLA) molecules with antigen-specific T cell receptors (TCR) and are the key effector cells of the adaptive immune response. In contrast, NK cells lack antigen-specific receptors and are regulated by the balance of signals from activating and inhibitory receptors. These two types of cells cooperate and complement each other in eliciting host immune response to cancer and mediating immune surveillance. Moreover, these cells play a crucial role in antitumor immunotherapy, including monoclonal antibodies (mAbs), bispecific T cell engagers (BiTe), as well as adoptive transfer of chimeric antigen receptor (CAR)-modified cytotoxic cells.

Download or read book Advances in Tumor Immunology and Immunotherapy written by Joseph D. Rosenblatt and published by Springer Science & Business Media. This book was released on 2013-10-25 with total page 369 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent advances in understanding of fundamental immunology have created new insights into the dynamic interactions between tumors and the immune system. This includes new understanding of T- and B-cell interaction, immune inhibitory mechanisms including the biology of T regulatory cells, myeloid suppressor cells, and dendritic cell subsets. Enhanced understanding of mechanisms underlying T-cell anergy such as arginine deprivation, immunosuppressive cytokines, defective innate and interferon response pathways, and NKG2D downregulation have all provided new insight into suppression of anti-tumor immunity and tumor evasion. In addition to emerging understanding of tumor evasion, new immune targets such as CTLA4 blockade, NK stimulatory receptors, manipulation of the antigen processing and presentation, cytokine and costimulatory responses all provide new possibilities for enhancing anti-tumor immunity even in tumors previously felt to be resistant to immune attack. Several of these strategies have already been realized in the clinic. The volume will explore evolving paradigms in antigen presentation, dendritic cell biology, the innate response and immunosuppressive mechanisms, and emerging strategies for manipulation of the immune system for therapeutic benefit that have realized success in neuroblastoma, leukemia, melanoma, lung cancer, and allogeneic transplantation. Early successes as well as failures will be highlighted to provide a snapshot of the state of clinical immunotherapy with an eye to future possibilities such as combination therapies, adoptive T-cell transfer, and the retargeting of immune cells via T-cell receptor engineering.

Download or read book Advances in Immunity and Cancer Therapy written by P. K. Ray and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 526 pages. Available in PDF, EPUB and Kindle. Book excerpt: The rapid and continuous upsurge of interesting data in the subject of tumor immunology necessitates the publication of an annual series to furnish the updated materials to the students, researchers, and clinicians in this rapidly advancing field. Concepts and methodologies are ever changing. Also, current research in tumor immunology promises to offer breakthroughs in the future. Important is the need to communicate to the right people the exact role of immunodiagnostic methods and immunological intervention in cancer preven tion and treatment. The role of immunotherapy in combination with conven tional modalities of treatment needs to be understood in its proper perspective. Oncogene, interferon, lymphokines, monoclonal antibodies, natural killer cells, platelet-mediated cytotoxicity of antibody-coated target cells, suppressor cells, platelet-derived factors, plasma-blocking factors, control of suppressor cell func tion, abrogation of plasma-blocking factors, and so forth, are some of the areas that are continually advancing. Progress in these areas will have implication in cancer therapy. Further, it is already understood that if immunocompetence of the host can be maintained at a reasonably good level, there exists the potential to increase the therapeutic indexes of conventional modalities of treatment. This series will attempt to present updated information in all these areas based on con tributed and solicited articles.

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 Novel Antigen Delivery Approaches for Priming T Cell mediated Immune Responses written by Dirk Brockstedt and published by Herbert Utz Verlag. This book was released on 1998 with total page 116 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 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 Adoptive Cell Transfer written by and published by Academic Press. This book was released on 2022-07-05 with total page 206 pages. Available in PDF, EPUB and Kindle. Book excerpt: Adoptive Cell Transfer, Volume 370 in the International Review of Cell and Molecular Biology series highlights advances in the field, with this new volume presenting interesting chapters written by an international board of authors who expound on topics such as the Impact of tumor microenvironment on Adoptive Cell Transfer activity, Dendritic Cell Transfer, CAR-T Cell dysfunction and exhaustion, NK Cell-based cancer immunotherapy, Enabling CAR-T cells for solid tumors: rage against the suppressive tumor microenvironment, Improving Adoptive T-Cell therapy with cytokines administration, and What will (and should) be improved in Immunotherapy with CAR? - Publishes only invited review articles on selected topics - Authored by established and active cell and molecular biologists and drawn from international sources - Offers a wide range of perspectives on specific subjects

Download or read book Is the Recent Burst of Therapeutic Anti Tumor Antibodies the Tip of an Iceberg written by Leonor Kremer and published by Frontiers Media SA. This book was released on 2018-03-27 with total page 305 pages. Available in PDF, EPUB and Kindle. Book excerpt: The high effectiveness of antibodies as anti-tumor therapeutic agents has led to a burst of research aiming to increase their therapeutic applications by the use of antibodies against new targets, new antibody formats or new combinations. In this e-book we present relevant research depicting the current efforts in the field.

Download or read book Cancer Immunotherapy Principles and Practice Second Edition written by Lisa H. Butterfield, PhD and published by Springer Publishing Company. This book was released on 2021-08-25 with total page 1339 pages. Available in PDF, EPUB and Kindle. Book excerpt: Thoroughly updated to reflect major advances in the field of immuno-oncology, this second edition of Cancer Immunotherapy Principles and Practice, from the Society for Immunotherapy of Cancer (SITC), remains the definitive resource for information on tumor immunology and cancer immunotherapy treatments. An essential reference for both novice and experienced cancer researchers, oncologists, and related practitioners alike, the book not only guides readers through the fundamental scientific principles of the field all the way to translational and practical clinical applications for treating and managing oncologic disease, but also provides a comprehensive understanding of the regulatory processes that support the safe and effective delivery of immunotherapy to patients with cancer. The expanded and updated second edition now spans 68 chapters, including 12 new chapters, covering major topics and innovations that have shaped the rapid development of immunotherapy and its ascension into the standard of care as first-line treatment for a growing number of disease settings. New to this edition are chapters with deeper insight into our understanding of cancer genomics and determinants of response, immunogenic cell death, cancer and stromal cell-intrinsic pathways of immune resistance, cancer immune exclusion, adoptive cell therapy, metabolomics, tumor mutation burden, immunotherapy in combination with radiation therapy, synthetic biology, and more. Complete with detailed illustrations, tables, and key points for targeted reference, Cancer Immunotherapy Principles and Practice, Second Edition is the most comprehensive and authoritative resource for scientists and clinicians looking to expand their knowledge base of this dynamic field. Key Features: Offers key insights and perspectives on cancer immunology and immunotherapy treatments from renowned experts in the field Covers the basic principles and science behind cancer immunotherapy and tumor immunology Includes treatment strategies for a vast array of available immunotherapy classes and agents, such as cytokine therapies, oncolytic viruses, cancer vaccines, CAR T therapies, and combination immunotherapies Provides essential information on FDA-approved immunotherapies, including clinical management and outcome data related to response rates, risks, and toxicities Discusses special considerations for immunotherapy in the context of specific disease settings, including skin cancers, genitourinary cancers, gastrointestinal cancers, hepatocellular carcinomas, gynecologic malignancies, breast cancers, lung cancers, head and neck cancers, brain tumors, sarcomas, pediatric cancers, and treatments combined with radiation therapy Clarifies the complex regulatory aspects behind the development and approval of immunotherapy drugs