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This volume presents the most complicated and powerful cancer biotherapies developed. It provides an overview of human immune system function and the mechanisms by which adoptive cellular immunotherapies (ACI) harnesses the activity. The volume provides a vision on the developments in ACI.
This volume presents the most complicated and powerful cancer biotherapies developed. It provides an overview of human immune system function and the mechanisms by which adoptive cellular immunotherapies (ACI) harnesses the activity. The volume provides a vision on the developments in ACI.
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.
Cancer research has progressed enormously in recent years. This review volume will address recent findings in the area of T-cell therapy for cancer, including use of tumour infiltrating lymphocytes (TILs) as a therapy for melanoma, choice of target antigens, advances in engineered receptors, methods of gene transfer to T cells, review of cell processing methods and clinical trial design. Written by leadings scientists in the field, this up-to-date review on cancer research will be an important reference source to the researchers and healthcare professionals in the field.
Cancer treatments that are based on the reactivation, expansion, or mobilisation of the immune system, such as adoptive cellular therapies and immune-checkpoint blockade, have achieved long-lasting anti-tumour responses in cancer patients. However, there is still a high proportion of patients that do not benefit from these treatments. This highlights the need for more effective therapies. Based on the notion that adoptive cell therapies do work and are likely limited in vivo by the activation of immune modulatory pathways, this project focused on ablating negative regulation and increasing the intra-tumoural effector activity of tumour-reactive T cells. Specifically, my project aimed to genetically modify tumour infiltrating T cells by knocking-out the expression of immune- checkpoints on their surface so as to render them resistant to checkpoint inhibition, thus generating potent and long-lasting anti-tumour immunity. For this purpose, the CRISPR/Cas9 technology was used to genome edit tumour-reactive T cells using primary human tumour-infiltrating lymphocytes (TILs) obtained from melanoma and non-small-cell lung carcinoma (NSCLC) patients. The project initially focused on the generation of PD1-deficient tumour- reactive T cells as a proof of concept, as targeting this pathway with antibodies has shown clear efficacy in the clinic. Following the generation of PD1-deficient gene edited T cells, we developed LAG3-deficient and TIGIT-deficient tumour-reactive T cells, as well as T cells that were deficient for both PD1 and LAG3 expression. In sum, the overall purpose of this project was to utilise cutting edge gene editing tools to engineer tumour-reactive lymphocytes and render them resistant to checkpoint inhibition. The results from this work have established a clinically relevant pipeline for the generation of potent adoptive cell therapy products for the treatment of cancer.
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.
This volume provides a comprehensive, state-of-the art review of the field of cell therapy. The volume begins with an overview of the breadth of the field and then turns to overviews of imaging technologies that can aid in both safety and efficacy evaluations. The book then turns to numerous contributions detailing the rapidly growing field of stem cell therapies. These sections cover our understanding of the natural roles of stem cells in biology and human disease and then touches on several of the more prominent areas where stem cells are moving rapidly into clinical evaluation including neurodegenerative diseases, muscular dystrophy, cardiac repair, and diabetes. The volume concludes with contributions from experts in oncology, ophthalmology, stem cells, 3-D printing, and biomaterials where the convergence of expertise is leading to unprecedented insights into how to minutely control the in vivo fate and function of transplanted and/or endogeneously mobilized cells. Finally, the book provides insights into the pivotal relationship between academic and industrial partnerships. This volume is designed to touch on the major areas where the field will make its greatest and most immediate clinical impacts. This text will provide a useful resource for physicians and researchers interested in the rapidly changing filed of cell therapy.