Immunotherapy with genetically engineered immune cell products is a transformative treatment modality with potential applications in various fields of medicine. A prime example is chimeric antigen receptor (CAR)-modified T cells in hematology and oncology, and the advent of CAR T cell therapies to treat infectious diseases, autoimmune disorders, and cardiovascular diseases. The medical need and demand from patients and caregivers require radical innovations to accelerate and improve pre-clinical development and clinical translation, provision of gene-transfer vectors, and immune cell product manufacturing as well as a critical reflection and discussion on ethical and socioeconomic aspects. The goal of this special issue of Frontiers in Immunology is to provide a comprehensive and multi-faceted view on the current state-of-the-art, imminent and future directions the field is taking in order to accelerate the pre-clinical development, clinical translation, and manufacturing of CAR T cells, increase access and sustainability of CAR T cell therapy for health care systems (in developed and in developing countries). This special issue will focus on the medical and scientific dimension incl. approved and emerging indications, new areas in medicine, advanced gene-transfer and gene-editing technologies, innovations in pre-clinical assessment (efficacy, toxicology, genomic safety), innovations in scalable automated manufacturing (bioprocessing), the implementation of high content data acquisition, machine learning and artificial intelligence, innovations in clinical trial design; and consider the ethical, socioeconomic and societal dimension of CAR T cells in particular and gene-engineered immune cell therapy in general.

Essentials of Translational Pediatric Drug Development: From Past Needs to Future Opportunities provides integrated and up-to-date insights relevant for both translational researchers and clinicians active in the field of pediatric drug development. The book covers all key aspects from different stakeholder perspectives, providing a literature overview and careful reflection on state-of-the-art approaches. It will be an ideal guide for researchers in the field who are designing and performing high quality, innovative pediatric-adapted drug development by helping them define needs/challenges and possible solutions that advance and harmonize pediatric drug development.Despite the broad consensus that children merit the same quality of drug treatment as any other age group, children remain frequently neglected during drug research and development. Even with the adoption of multiple legislations addressing this problem, the lack of efficacy and safety data of marketed as well as newly developed drugs still remain in the pediatric population. Covers both theoretical and practical aspects of translational pediatric drug development Approaches the topic from different stakeholder perspectives (academics, industry, regulators, clinicians and patient/parent advocacy groups) Offers best practices and future perspectives for the improvement of translational pediatric drug development

Cell and gene therapies have become the third major drug modality in pharmaceutical medicine of the 21st century after low molecular weight and antibody drugs. The gene therapy (GTx) field is rapidly advancing, and yet there are still fundamental scientific questions that remain to be answered. Development of GTx products poses unique challenges and opportunities for drug developers. However, there is lack of a systematic exposition of the GTx product development and the pivotal role of the biostatistician in this process. Development of Gene Therapies: Strategic, Scientific, and Regulatory, and Access Considerations attempts to summarize the current state-of-the-art strategic, scientific, statistical, and regulatory aspects of GTx development. Intended to provide an exposition to the GTx new product development through peer-reviewed papers written by subject matter experts in this emerging field, this book will be useful for researchers in gene therapy drug development, biostatisticians, regulators, patient advocates, graduate students, and the finance and business development community . Key Features: A collection of papers covering a wide spectrum of topics in gene therapies (GTx), written by leading subject matter experts An exposition of the core principles of GTx product development, emerging business models, industry standards, best practices, and regulatory pathways An exposition of statistical and innovative modeling tools for design and analysis of clinical trials of GTx Insights into commercial models, access hurdles, and health economics of gene therapies Case studies of successful GTx approvals from core team members that developed the first two FDA-approved AAV gene therapies: Luxturna and Zolgensma A discussion of potential benefits and hurdles to be overcome for GTx in coming years from a multi-stakeholder perspective

Multi-stakeholder collaborations involving partners from public and private sectors are essential to address global health challenges and to move precision medicine forward. This eBook assembles a collection of papers which either illustrate recent achievements or discuss new perspectives offered by public-private partnerships in healthcare. Publisher’s note: In this 2nd edition, the following article has been added: Laverty H and Meulien P (2019) The Innovative Medicines Initiative −10 Years of Public-Private Collaboration. Front. Med. 6:275. doi: 10.3389/fmed.2019.00275

This book provides a detailed description of all kinds of therapeutic antibodies including IgGs, IgAs, IgEs, and IgMs, bispecific antibodies, chimeric antigen receptor antibodies, and antibody fragments. Details about how each of these antibodies interact with their ligands, the immune system, and their targets are provided. Additionally, this book delves into the details of antibody, Fc, and variable chain structures, and how subtle changes in structure, charge, flexibility, post-translational modification, and the ability to bind to natural antibody ligands can result in a significant impact on antibody activity and functionality. Finally, the book explains the critical quality attributes of modern therapeutic antibodies and how to ensure that antibodies entering development have the best possible chance of success.

the latest release in this ongoing, well-regarded serial, provides invaluable information on the exciting and fast-moving field of cancer research, with this updated edition covering chapters on A bioinformatic-driven prediction of MDA9 transcriptional variants' roles in cancer progression and treatment, Redox, cysteines, and kinases - A triad sustaining myeloid leukemia, The RAF cysteine-rich domain: structure, function, and role in disease , Membrane Potential: a new hallmark of cancer, Recent Advances and Progress in Immunotherapy of Solid Cancers, and much more.Other sections explore Precision Medicine: Non-Invasive Therapeutic Agent Delivery with Focused Ultrasound and Microbubbles and Anti-Cancer Activity of Capsaicin and its Analogs in Gynecological Cancers. - Provides the latest information on cancer research - Offers outstanding and original reviews on a range of cancer research topics - Serves as an indispensable reference for researchers and students alike

This new edition presents a fully-updated and expanded look at current Good Manufacturing Practice (cGMP) for cell therapy products. It provides a complete discussion of facility design and operation including details specific to cord blood banking, cell processing, vector production and qualification of a new facility. Several chapters cover facility infrastructure including cleaning and maintenance, vendor qualification, writing a Standard Operating Procedure, staff training, and process validation. The detailed and invaluable product information covers topics like labelling, release and administration, transportation and shipment, et al. Further chapters cover relevant topics like writing and maintaining investigational new drug applications, support opportunities in North America and the European Union, commercial cell processing and quality testing services, and financial considerations for academic GMP facilities. A chapter on future directions rounds out Cell Therapy: cGMP Facilities and Manufacturing making it essential reading for any cell therapy professional involved in the development, use, or management of this type of facility.

Translational Medicine: Optimizing Preclinical Safety Evaluation of Biopharmaceuticals provides scientists responsible for the translation of novel biopharmaceuticals into clinical trials with a better understanding of how to navigate the obstacles that keep innovative medical research discoveries from becoming new therapies or even making it to clinical trials. The book includes sections on protein-based therapeutics, modified proteins, oligonucleotide-based therapies, monoclonal antibodies, antibody–drug conjugates, gene and cell-based therapies, gene-modified cell-based therapies, combination products, and therapeutic vaccines. Best practices are defined for efficient discovery research to facilitate a science-based, efficient, and predictive preclinical development program to ensure clinical efficacy and safety. Key Features: Defines best practices for leveraging of discovery research to facilitate a development program Includes general principles, animal models, biomarkers, preclinical toxicology testing paradigms, and practical applications Discusses rare diseases Discusses "What-Why-When-How" highlighting different considerations based upon product attributes. Includes special considerations for rare diseases About the Editors Joy A. Cavagnaro is an internationally recognized expert in preclinical development and regulatory strategy with an emphasis on genetic medicines.. Her 40-year career spans academia, government (FDA), and the CRO and biotech industries. She was awarded the 2019 Arnold J Lehman Award from the Society of Toxicology for introducing the concept of science-based, case-by-case approach to preclinical safety evaluation, which became the foundation of ICH S6. She currently serves on scientific advisory boards for advocacy groups and companies and consults and lectures in the area of preclinical development of novel therapies. Mary Ellen Cosenza is a regulatory toxicology consultant with over 30 years of senior leadership experience in the biopharmaceutical industry in the U.S., Europe, and emerging markets. She has held leadership position in both the American College of Toxicology (ACT) and the International Union of Toxicology (IUTOX) and is also an adjunct assistant professor at the University of Southern California where she teaches graduate-level courses in toxicology and regulation of biologics.

A comprehensive review of the challenges that exist in patient accessibility to regenerative medicines (RMs), presenting clinical trials, marketing authorization, HTA, pricing, reimbursement, affordability, payment and partnership agreements of RMs and commercialization. Specfically, we investigated how COVID-19 has impacted the RM industry by elaborating on the disruptions it caused but also the new opportunities it brought. The ultimate goal of this work is to make strategic recommendations for manufacturers and decisions-makers on effective strategies to address the above obstacles and facilitate patient access to promising regenerative medicines. FEATURES Regenerative medicine (RM) is an emerging interdisciplinary field aiming to replace or regenerate human cells, tissues, or organs in order to restore normal function. RM holds the promise of revolutionizing treatment in the 21st century. RMs bring new hope for some previously untreatable diseases, as well as holding promise for the treatment of common chronic diseases. Rapid advancements in biotechnology and improved understanding of disease pathophysiology have attracted tremendous interests in the development of RMs. Discusses the high cost of RMs which may challenge the sustainability of healthcare insurers (public and private).