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Since the publication of the second edition of this book in 2004, gene therapy and cell therapy clinical trials have yielded some remarkable successes and some disappointing failures. Now in its third edition, Gene and Cell Therapy: Therapeutic Mechanisms and Strategies assembles many of the new technical advances in gene delivery, clinical applications, and new approaches to the regulation and modification of gene expression. New Topics Covered in this Edition: Gene and Cell Therapies for Diabetes and Cardiovascular Diseases Clinical Trials Human Embryonic Stem Cells Tissue Engineering Combined with Cell Therapies Novel Polymers Relevant Nanotechnologies SiRNA Therapeutic Strategies Dendrimer Technologies Comprised of contributions from international experts, this book begins with a discussion of delivery systems and therapeutic strategies, exploring retroviral vectors and adenovirus vectors, as well as other therapeutic strategies. The middle section focuses on gene expression and detection, followed by an examination of various therapeutic strategies for individual diseases, including hematopoietic disorders, cardiovascular conditions, cancer, diabetes, cystic fibrosis, neurological disorders, and childhood-onset blindness. The final section discusses recent clinical trials and regulatory issues surrounding the new technology. This compendium is assembled by noted molecular biologist and biochemist Nancy Smyth Templeton. Baylor College of Medicine and several other institutions have used Dr. Templeton’s non-viral therapeutics in clinical trials for the treatment of lung, breast, head and neck, and pancreatic cancers, as well as Hepatitis B and C. She continues to work at the forefront of research in gene and cell therapies. Her contributions, as well as those contained in this volume, are sure to advance the state of the art of these revolutionary life-saving technologies.

A Roadmap to Non-hematopoietic Stem Cell-Based Therapeutics: From the Bench to the Clinic is a resource that provides an overview of the principles of stem cell therapy, the promises and challenges of using stem cells for treating various clinical conditions, and future perspectives. The overall goal is to facilitate the translation of basic research on stem cells to clinical applications. The properties of stem cells from various sources are reviewed and the advantages and disadvantages of each for clinical use are discussed. Modifying stem cell properties through preconditioning strategies using physical, chemical, genetic, and molecular manipulation to improve cell survival, increase cell differentiation potential, enhance production of paracrine factors, and facilitate homing to the site of injury or disease upon transplantation are reviewed. Various routes of stem cell administration and dosing, and the duration of effects, are explored. Individual chapters are written by experts in the field and focus on the use of stem cells in treating various degenerative diseases, autoimmune diseases, wound healing, cardiovascular disease, spinal cord injury, oral and dental diseases, and skeletal disorders. Finally, experts in the regulatory arena discuss mechanisms used in different countries for approving the use of stem cells to treat diseases and many common issues that are typically encountered while seeking approval for this class of therapeutic agent. Offers advanced students, as well as new researchers, an overview of the principles of stem cell therapy Discusses a wide array of pressing clinical issues with stem cell-based therapies so that new ideas in the laboratory can be efficiently translated to the clinic through better designed clinical trials Helps clarify current regulatory mechanisms so that the safe use of stem cells for treating a variety of diseases can move forward Fosters cross-disciplinary dialogue between research scientists and physicians to accelerate the safe implementation of efficacious cell therapies

CONTEXT: In ZUMA-1 (NCT02348216), axicabtagene ciloleucel (axi-cel), an anti-CD19 chimeric antigen receptor (CAR) T cell therapy, demonstrated significant benefit in patients with refractory large B cell lymphoma with an objective response rate (ORR) of 82% (complete response [CR], 58%; Neelapu & Locke, et al. NEJM. 2017). These results supported the approval of axi-cel by the US FDA for the treatment of adult patients with relapsed or refractory large B cell lymphoma after u22652 prior lines of systemic therapy.OBJECTIVE: We assessed outcomes of axi-cel by prior lines of therapy (LoT) in patients from Phases 1 and 2 of ZUMA-1.DESIGN: Patients with refractory large B cell lymphoma were leukapheresed and received 2u00d7106 CAR T cells/kg after low-dose conditioning (Neelapu & Locke, et al. NEJM 2017). Patients were evaluated by number of prior LoT: 2-3 vs u22654. Autologous stem cell transplant (ASCT) was considered a prior LoT.RESULTS: As of 8/11/17, median follow-up was 15.4 months for the 108 patients treated with axi-cel. Sixty-two patients (57%) had 2-3 prior LoT, and 43 (40%) had u22654. Patients with 2-3 and u22654 prior LoT had median ages of 60 and 55 years; 65% and 47% had ECOG performance status of 1, 18% and 42% had prior ASCT, and 76% and 93% had disease stage III/IV, respectively. ORRs were 94% (CR, 65%) and 67% (CR, 53%) for patients with 2-3 and u22654 prior LoT, respectively, and 44% and 42% of patients had ongoing responses as of the data cutoff. Overall survival (OS) at 12 months was 65% and 51% for patients with 2-3 and u22654 prior LoT, respectively. Grade u22653 treatment-emergent adverse events were reported for nearly all (100% and 93%) patients with 2-3 and u22654 LoT, with similar rates of Grade u22653 cytokine release syndrome (11% and 12%) and neurologic events (32% and 30%). There were 1 and 3 Grade 5 adverse events unrelated to disease progression in the 2-3 and u22654 LoT groups, respectively.CONCLUSIONS: Axi-cel demonstrated long-term clinical benefit for patients with refractory large B cell lymphoma regardless of the number of prior LoT.FUNDING SOURCE: Kite, a Gilead Company.

This Open Access edition of the European Society for Blood and Marrow Transplantation (EBMT) handbook addresses the latest developments and innovations in hematopoietic stem cell transplantation and cellular therapy. Consisting of 93 chapters, it has been written by 175 leading experts in the field. Discussing all types of stem cell and bone marrow transplantation, including haplo-identical stem cell and cord blood transplantation, it also covers the indications for transplantation, the management of early and late complications as well as the new and rapidly evolving field of cellular therapies. This book provides an unparalleled description of current practices to enhance readers' knowledge and practice skills. This work was published by Saint Philip Street Press pursuant to a Creative Commons license permitting commercial use. All rights not granted by the work's license are retained by the author or authors.

Cell Therapy: cGMP Facilities and Manufacturing is the source for a complete discussion of facility design and operation with practical approaches to a variety of day-to-day activities, such as staff training and competency, cleaning procedures, and environmental monitoring. This in-depth book also includes detailed reviews of quality, the framework of regulations, and professional standards. It meets a previously unmet need for a thorough facility-focused resource, Cell Therapy: cGMP Facilities and Manufacturing will be an important addition to the cell therapy professional’s library. Additional topics in Cell Therapy: cGMP Facilities and Manufacturing...Standard operating procedures - Supply management - Facility equipment - Product manufacturing, review, release and administration - Facility master file.

The major advances in the field of biotechnology and molecular biology in the twenty-first century have led to a better understanding of the pathophysiology of diseases. A new generation of biopharmaceuticals has emerged, including a wide and heterogeneous range of innovative cell and gene therapies. These therapies aim to prevent or treat chronic and serious life-threatening diseases, previously considered incurable. This book describes the evolution and adaptation of the regulatory environment to assess these therapies in contrast with the resistance of health technology assessment (HTA) agencies and payers to acknowledge the specificity of cell and gene therapies and the need to adapt existing decision-making frameworks. This book provides insights on the learnings from the experience of current cell and gene therapies (regulatory approval, HTA, and market access), in addition to future trends to enhance patient access to these therapies. Key Features: Describes the potential change of treatment paradigm and the specificity of cell and gene therapies, including the gradual move from repeated treatment administration to one-time single administration with the potential to be definite cure Highlights the challenges at the HTA level Discusses the affordability of future cell and gene therapies and the possible challenges for health insurance systems Provides potential solutions to address these challenges and ensure patient access to innovation while maintaining the sustainability of healthcare systems

Sparked by a new understanding that the development of tissues is not restricted to the embryonic phase of development and thus that regeneration of tissues can occur in adults, the emerging field of stem cell therapy has grown exponentially in the last several years. Crucially, the research and findings associated with stem cell research overlap into many other areas, such as basic cell biology, molecular biology and hematology, and the proliferation of clinical studies involving stem cell research is gradually crossing over into the practice of medicine as many patients may become candidates for such novel treatments. As a response to this, Guide to Cardiac Cell Therapy is a comprehensive but understandable resource that makes this exciting field accessible to clinical practitioners. Bridging the gap between basic science and practice, it is a useful introduction to the area as well as a cutting-edge update of the developments in stem cell therapy as applied to cardiovascular disease.