Claudio mussolino, institute for transfusion medicine and gene therapy, medical centeruniversity of freiburg, breisacherstr. In practice, cart cell process validation can present unique challenges in each stage of validation. Gene therapy for transfusiondependent thalassemia, an inherited blood disorder, produced positive outcomes in an interim analysis of two international phase 12 clinical trials, according to the results published in new england journal of medicine. The institutes research efforts focus on the development and evaluation of safe platforms for the manufacturing of advanced therapy medicinal products. Originally envisioned as a treatment solely for inherited disorders, gene therapy is now being applied to acquiredconditions,aconceptbestillustratedby genetic engineering of t cells for cancer immunotherapy. Gene therapy applications to transfusion medicine request pdf. Sponsorship and funding for gene therapy trials in the. The global gene therapy market size was estimated at usd 1. Transfusion medicine and the development of gene therapy. Jan 14, 2019 department of transfusion medicine fellowship in transfusion medicine. Previously, clinical investigators thought that the human genetic.
Rossis principles of transfusion medicine wiley online. A small study finds promise for using gene therapy to treat patients with betathalassemia, a blood condition that can cause severe anemia. The scope of the journal encompasses basic science, practical aspects, laboratory developments. Gene marking marker genes are of great value for the accurate followup, both in vitro and in vivo, of transduced cells. At87q gene could substitute for longterm redcell transfusions in a patient with. Pdf transfusion medicine and molecular genetic methods. Original article from the new england journal of medicine gene therapy in patients with transfusiondependent.
The scope for thalassemia gene therapy by disruption of. The effects of current gene therapy approaches are limited to the treated patients cells. Gene therapy applications to transfusion medicine rossis. The basic concept of gene therapy is to introduce a gene with the capacity to cure or prevent the progression of a disease. Gene therapy is the basis for the plotline of the film i am legend and the tv show will gene therapy change the human race in 1994, gene therapy was a plot element in the erlenmeyer flask, the firstseason finale of the xfiles. Karl skorecki, eithan galun, in goldmans cecil medicine twenty fourth edition, 2012. A new treatment for children and adults with a rare, inherited form of vision loss is the first gene therapy approved in the united states for a genetic disease. Thalassemia patients who are transfusion dependent april 25, 2018. Nine of the patients had the most severe form of betathalassemia, with two copies of genes that eliminate betaglobin production. After previously establishing that lentiviral transfer of a marked. Post infusion it was found that the patients had 2025% circulating genecorrected t cells, some improvement in immune function and resolution of clinical symptoms. Over 90% of the gene therapy dedicated capacity is commercially owned space. At87qglobin gene, formerly known as lentiglobin bb305 is a treatment for beta thalassemia, a rare and potentially debilitating blood disorder.
Cart cell manufacturing facilities must validate any process, policy, or procedure that has potential to impact the quality of the product. In addition, in the case of all three disorders, the normal gene has been cloned and is available. Modified genes are not passed on from one generation to the next. Learn about approaches to and issues surrounding gene therapy. The analysis highlights the distribution of the capabilities on the basis of the.
Relevant aspects in the advances in transfusion medicine using gene. Immunotherapy and gene transfer in the treatment of the oncology patient. Gene therapy has the potential to revolutionise treatment for patients with haemophilia. Gene therapy is a technique that uses genetic material a piece of dna for the longterm treatment of genetic disorders. Gene therapy is mainly driven by the potential exhibited by car tcell usage which has gained significant attention from commercial and noncommercial sponsors as a new business model. Although the field of gene therapy has experienced significant setbacks and limited success, it is one of the most promising and active research fields in medicine. During process design, understanding and control of. Gene therapy reduces transfusion dependence in patients. The twoyear fellowship training program prepares physicians for a career in transfusion medicine, providing experience in clinical, technical, investigational and administrative aspects of the field in preparation for the certifying examination in transfusion medicine blood banking offered by the american board of pathology.
The implementation of globin gene transfer for the treatment of severe. In the most severe form of beta thalassemia, transfusiondependent beta thalassemia, affected individuals are dependent on. Intrabone hematopoietic stem cell gene therapy for adult. Genome editing in transfusion medicine claudio mussolino address correspondence to. The experimental treatment is in early development. Interest in this therapeutic modality is based on the potential for treatment and cure of some of the most malignant and devastating diseases affecting humans. Gene therapy guidelines for the management of transfusion. Gene therapy in patients with transfusiondependent. Institute for transfusion medicine and gene therapy, medical centeruniversity of freiburg, 79106 freiburg, germany. He will be transitioning to a role as an assistant professor in the department of pathology at mt sinai hospitalicahn school of medicine with a focus on transfusion medicine, apheresis and cell therapy. Jan 21, 2019 in a phase 12 clinical trial, gene therapy with autologous hematopoietic stem cells significantly reduced transfusion requirement in adults and children with transfusion dependent. Blood groups, genetic marker, human platelet antigen and. Transfusion is an important medical treatment, especially in trauma cases.
Cancer is the most common disease in gene therapy clinical trials. Department of transfusion medicine nih clinical center. Westhoff, sbb, phd executive scientific director immunohematology and genomics national center for blood group genomics 2 objectives. After gene therapy, this group experienced a 74% reduction in annual blood transfusions. There has been an increase in the dedicated gene therapy manufacturing space 3,889m2 in 2019 from 3,619m2 in 2018 and the. Apr 18, 2018 gene therapy for transfusiondependent thalassemia, an inherited blood disorder, produced positive outcomes in an interim analysis of two international phase 12 clinical trials, according to the results published in new england journal of medicine. Rossis principles of transfusion medicine wiley online books. Cellular therapy is quickly becoming an integral part of transfusion medicine. Gene therapy encompasses multiple approaches to manipulate genetic material in an effort to treat specific diseases, including replacing a mutated or defective gene with a healthy one, introducing a new gene to help fight disease, or editing an existing gene to change its function 1. Department of transfusion medicine fellowship in transfusion medicine. Gene therapy thalassemia has already become a clinical reality using lentiviral lv vectors to replace key elements of the. Genome editing in transfusion medicine stem cells and.
Human gene therapy has been attempted on somatic body cells for diseases such as cystic fibrosis and cancer. The worlds first gene therapy product was licensed in china in 20041 and the first in europe is expected to be licensed in the next few years. Gene therapy in clinical medicine postgraduate medical. A potential role of transfusion medicine is expected because cell therapy target for gene transfer, a new medical practice, was born in blood transfusion services. Gene therapy for blood disorder ends need for transfusions. Gene therapy and cell therapy also offer a promising alternative or adjunct treatment for symptoms of many acquired diseases, such as cancer, rheumatoid arthritis, diabetes, parkinsons disease, alzheimers disease, etc. Apr 19, 2018 after previously establishing that lentiviral transfer of a marked.
Bone marrow failure due to disease, cytotoxic therapy or irradiation 39 immunological disorders use of immunoglobulin 42 therapeutic plasma exchange 43 section 5 immunoglobulin for prevention of infection 47 handbook of transfusion medicine vi. Gene therapy reduces transfusion dependence in patients with. Investigations of stem cellbased approaches for the treatment of other. Handbook of transfusion medicine optimal blood use. Rossis principles of transfusion medicine is the most comprehensive and practical reference on transfusion science and medicine available.
Efficacy of st400 for treatment of transfusiondependent beta. Clinical gene therapy in vitro focuses on gene transfer to autologous hematopoietic stem cells hscs for the treatment of various diseases, especially hematologic. Institute for transfusion medicine and gene therapy. The remainder of the gene therapy cleanroom space is distributed between uk academia and the nhs with 8 cleanrooms per site being the median. Gene therapy for transfusion dependent betathalassemia. The first attempt at modifying human dna was performed in 1980 by martin cline, but the first successful nuclear gene transfer in humans, approved by the national institutes of health, was performed in. This chapter focuses on the possible applications of gene therapy to transfusion medicine. Recent clinical studies have found that single infusions of t cells engineered with. The focus of cancer gene therapy has been in melanoma, prostrate, ovarian and leukemia 3.
Gene therapy in sickle cell disease 10 november 2018 kevin kuo, md, msc, frcpc clinicianinvestigator and assistant professor red blood cell disorders program, therapeutic apheresis program division of medical oncology and hematology, university health network division of hematology, department of medicine, university of toronto. Homologous cellular therapy products are those products that are used to repair, reconstruct, replace or supplement a recipients cells or tissue and perform the same basic function in the recipient as in the donor. Transfusion medicine and molecular genetic methods ncbi. Sponsorship and funding for gene therapy trials in the united. Lentiglobin gene therapy for patients with transfusiondependent. Dec 05, 2015 gene therapy reduces transfusion dependence in patients with betathalassemia major. Out of 22 patients aged 12 35 years, 15 patients achieved transfusionfree status, while. Transfusion independence and hmga2 activation after gene. For many years it has been proposed that genetic modification of human cells could be undertaken for therapeutic purposes. Gene therapy reduces transfusion dependence in patients with betathalassemia major. Gene therapy reduces need for transfusions in severe blood. These children underwent retroviral transduction of il2 expanded autologous peripheral blood t lymphocytes with a transgene encoding the ada gene. This research study includes the investigations done of the past progress, present ongoing market scenarios, and future prospects.
Pdf transfusion procedures are always complicated by potential genetic. Currently is a fellow in transfusion medicine and apheresis at yalenew haven. Gene therapy falls within the purview of transfusion medicine when it requires the infusion of either gene. Results were published in the new england journal of medicine on april 19, 2018. Weinberg phd, in transfusion medicine and hemostasis second edition, 20. Apr 18, 2018 a small study finds promise for using gene therapy to treat patients with betathalassemia, a blood condition that can cause severe anemia. The use of autologous modified stem cells for engraftment has the obvious advantage of providing hsct for all patients. Gene therapy falls within the purview of transfusion medicine when it requires the infusion of either.
Gene therapy for transfusion dependent betathalassemia tigetbthal the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Intrabone hematopoietic stem cell gene therapy for adult and. The scope for thalassemia gene therapy by disruption of aberrant regulatory elements. Gene therapy market size global industry growth report. Since 2017, the us food and drug administration fda has approved 4 gene therapies. Gene therapy for vision loss ophthalmology jama jama. It has been developed by bluebird bio and was given breakthrough therapy designation by the food and drug administration in february, 2015. The report titled,global gene therapy market professional insight survey and forecast to 2028is recently generated by.
Gene therapy also called human gene transfer is a medical field which focuses on the utilization of the therapeutic delivery of nucleic acid into a patients cells as a drug to treat disease. Gene therapy applications the pharmaceutical journal. Original article from the new england journal of medicine gene. The institute for transfusion medicine and gene therapy itg provides the university medical center with blood products and all transfusion and transplantation related diagnostic services. Original article from the new england journal of medicine gene therapy in patients with transfusion dependent. Gene therapy introduces a normal, functional copy of a gene into a cell in which that gene is defective. Over the next decade, the relevance of gene therapy to medical. The nih clinical center department of transfusion medicine dtm provides clinical services to support nih patients in need of blood component therapy, cellular therapy, therapeutic apheresis, and specialized laboratory diagnostics. Led by a world class editor team, including two pastpresidents of aabb, a past president of the american board of pathology and members of the fda blood products advisory committee, and international contributor team. Jun 10, 2019 genome editing in transfusion medicine claudio mussolino address correspondence to. In the most severe form of beta thalassemia, transfusion dependent beta thalassemia, affected individuals are dependent on blood transfusion, which is. Voretigene neparvovecrzyl, marketed as luxturna, is indicated for patients with confirmed biallelic rpe65 mutationassociated retinal dystrophy. Jan 14, 2020 department of transfusion medicine overview.
An analysis of the overall capacity and capability for cell and gene therapy manufacture within the uk. The goal of this therapy is thus to achieve transfusionindependence without. Gene therapy, introduction of a normal gene into an individuals genome in order to repair a mutation that causes a genetic disease. The worlds first gene therapy product was licensed in china in 20041 and the first in europe is expected to be licensed in. Listing a study does not mean it has been evaluated by the u. Does the evidence support the importance of high transfusion ratios of plasma and platelets to red blood cells in improving outcomes in severely injured patients. Betathalassemia treatment with gene therapy reduced. Westhoff, sbb, phd executive scientific director immunohematology and genomics.
783 1022 884 295 498 1258 974 307 524 1510 690 1112 1023 824 1175 1137 1436 1527 37 1475 1526 1482 578 413 500 578 523 463 1234 1456 263