Gene Therapy Advisory Committee Research Articles

Tvt CAR7: Phase 1 Clinical Trial of Base-Edited "Universal” CAR7 T Cells for Paediatric Relapsed/Refractory T-ALL

Background Genome editing can overcome HLA barriers to generate 'off-the-shelf’ CAR T cell therapies. Despite the success of CAR-T cell therapies in B-cell malignancies, the expression of shared T cell antigens has constrained the development of CAR T cells targeting T-cell malignancies, due to T cell fratricide. Targeted base editing using CRISPR guided cytidine deamination mediates highly precise C→U→T conversion which can directly disrupt gene expression without DNA breaks. This Phase I study will investigate the feasibility and safety of base edited (BE) allogeneic CAR T cells against CD7, disrupted for TCR, CD7 and CD52. The cells are used to secure remission ahead of allogeneic stem cell transplantation (allo-SCT). Investigational medicinal product (IMP) Two allogeneic healthy donor derived BE-CAR7 T cell banks were manufactured from steady state apheresis harvests using a semi-automated process under compliant conditions. Cells were activated with an anti-CD3/CD28 reagent (Transact) and electroporated with codon optimised base editor (coBE) mRNA and three single guide RNAs targeting TRBC, CD52 and CD7. Subsequent lentiviral transduction delivered CAR7 (59-62% efficiency) and magnetic bead processing depleted residual TCRαβ+ T cells (residual 0.1-0.3%). Highly efficient disruption of CD7 and CD52 (98-99%) was confirmed by sequencing. Cells were cryopreserved and QC tested by flow cytometry, ddPCR for copy number (3.1-3.6) and replication competent lentivirus was excluded. Anti-leukemic potency was confirmed in vitro and in human:murine chimera experiments. Trial sponsorship & approvals The TvT CAR7 study (ISRCTN15323014) is an open label, single centre, single arm and non-randomised clinical trial. The trial is sponsored by Great Ormond Street Hospital NHS trust and is supported by MRC, Wellcome Trust and NIHR. Clinical trial authorisation was provided by MHRA and ethical approval by a gene therapy advisory committee (GTAC) ahead of site initiation. Study aims and Objectives The study aims to establish the safety and feasibility of BE-CAR7 to induce molecular remission in children with relapsed/refractory (r/r) CD7-positive T-ALL, ahead of a planned allo-SCT. Assessments include incidence of adverse events, duration of remission, disease-free survival and overall survival. Expansion, persistence and elimination of BE-CAR7 cells and immune recovery after allo-SCT are monitored. Eligibility, treatment and recruitment The study opened on 14th April 2022 at Great Ormond Street Hospital recruiting children across the UK aged between 6 months and 16 years with r/r CD7+ T-cell malignancies quantifiable in bone marrow (>10-4 by flow or PCR). Exclusions include active uncontrolled infections, pre-existing GvHD or the detection of anti-HLA antibodies against the IMP. Eligible patients receive lymphodepletion with fludarabine (150 mg/sqm), cyclophosphamide (120 mg/kg) and alemtuzumab (1 mg/kg), followed by infusion of 0.2-2.0x106 BE-CAR7 T cells (maximum 5x104/kg TCRαβ T cells). Patients in molecular remission at day +28 proceed to allo-SCT, to remove BE-CAR 7 cells and promote immune reconstitution. The first subject was infused on 4th May 2022. Grade 2 CRS and grade 1 ICANS were observed, but no GvHD. Bone marrow assessment at d+28 revealed morphological remission without count recovery and with PCR-MRD <10-4 and the patient proceeded to reduced intensity allo-SCT as planned. This Phase 1 study aims to treat 10 children in the UK. Conclusion The study has demonstrated the feasibility of manufacturing "off-the-shelf” GMP-compliant base edited CAR7 T cells and is investigating their safety and efficacy against paediatric r/r T-ALL.

TT52CAR19: Phase 1 Trial of CRISPR/Cas9 Edited Allogeneic CAR19 T Cells for Paediatric Relapsed/Refractory B-ALL

Background‘Off-the-shelf’ CAR T cell therapies are being investigated as alternatives to autologous CAR therapy, and can be generated using genome editing from allogeneic donors. Strategies to address HLA barriers include disruption of T cell receptor expression to prevent GVHD and removal of cell surface HLA expression to obviate host mediated rejection, as well as removal of CD52 to create a survival advantage in the presence of Alemtuzumab. In this study, lentiviral mediated CAR19 expression is linked to CRISPR editing through the incorporation of CRISPR guide RNA sequences within the vector 3'Long terminal repeat (LTR). The trial is in progress using pre-manufactured batches of TT52CAR19 T cells.Investigational medicinal product (IMP)Three allogeneic non-HLA matched donor derived CAR19 T cell banks were manufactured from steady state apheresis harvests from registry volunteer donors, using a semi-automated process under compliant conditions. Cells were activated with anti-CD3/CD28 (Transact) reagent and transduced with a lentiviral vector, TT52CAR19, and dual guide sgRNA cassettes targeting the T cell receptor alpha chain (TRAC) and CD52 loci. Next electroporation of Cas9 mRNA elicited transient genome editing, and automated magnetic bead depletion removed remaining TCRαβ+ T cells (mean 0.7%) and enriched CAR19+ T cells (mean 92.8%). Cells were cryopreserved in aliquots suitable for dose-banding and subjected to release testing, including flow cytometry, quantification of copy number (mean 3.83) and exclusion of replication competent lentivirus. Potency of each bank was confirmed in human:murine chimera experiments.Trial sponsorship & approvalsThe study is open at a single site and is sponsored by Great Ormond Street Hospital NHS trust and is supported by the Medical Research Council and National Institute for Health Research. Clinical trial authorisation was awarded by the MHRA after expert review, and ethical approval including gene therapy advisory committee (GTAC) review, and health research authority (HRA) approval. The study is open label, single arm and non-randomised.Study aims and ObjectivesThe study aims to establish the safety and feasibility of TT52CAR19 for the induction of molecular remission in children with relapsed /refractory CD19-positive B-cell acute lymphoblastic leukaemia (B-ALL) within 28 days, ahead of planned allogeneic haematopoietic stem cell transplantation (allo-SCT). Assessments include time to remission, duration of remission, disease-free survival and overall survival. Expansion, persistence and elimination of TT52CAR19 cells and tracking of immune recovery after allo-SCT is monitored. Recording of complications and toxicities, including possible genotoxic side effects from CRISPR/Cas9 modification provides safety profile information.Eligibility, infusion and outcomesThe study plans to treat 10 children aged between 6 months and < 18 years with CD19+ B-ALL quantified at >10 -4 in marrow (by flow or PCR) who are ineligible for autologous therapy. To date 2/4 children screened were found eligible and proceeded to lymphodepletion comprising Fludarabine, Cyclophosphamide and Alemtuzumab followed by a single infusion of 0.8-2.0x10 6 CAR19 T cells and a maximum of 5x10 4/kg TCRαβ T cells. In both cases, there was no GVHD or CRS >grade 1 and recovery of neutrophil counts by d28. Molecular remission was achieved in one child, where TT52CAR19 cells persistence was tracked by chimerism and copy number until further conditioning and allo-SCT. This child remains in remission >6 months later.ConclusionsFeasibility of pre-manufacturing off-the-shelf CRISPR/Cas9 edited CAR19 T cells is demonstrated and the trial has provided first in human safety data and preliminary indications of potent anti-leukaemic activity in one of two subjects dosed. DisclosuresQasim: Autolus: Current equity holder in publicly-traded company; Novartis: Honoraria; Servier: Research Funding; Tessa: Membership on an entity's Board of Directors or advisory committees.

Editorial introductions

Editorial introductions

Editorial introductions

Current Opinion in Oncology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of psychiatry is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Bertrand Coiffier Bertrand Coiffier is Professor of Hematology at the Department of Hematology, Hospices Civils de Lyon and the University Claude Bernard, Lyon, France. After having specialized in hematology, Professor Coiffier has held a number of positions at the Hematology Department of the Edouard-Herriot Hospital, Lyon and then the Centre Hospitalier Lyon-Sud, Pierre-Benite. He is a member of several international societies, including the American Society of Hematology, the American Society of Clinical Oncology, the International Society for Medical Oncology, the European Haematology Association, and the European Society for Medical Oncology. Professor Coiffier is a founding member of the Group d’Etude des Lymphomes de l’Adulte (GELA) and has been President of the GELA since 2006. He has published over 300 papers in peer-reviewed journals. Anne-Sophie Michallet Anne-Sophie Michallet is a Doctor of Hematology at the Department of Hematology, Hospices Civils de Lyon and the University Claude Bernard, Lyon, France. After having specialized in hematology, she focused on lymphoproliferative disorders. She is a member of the French Group of Chronic Lymphocyic Leukemia (GFCLL and GOELAMS), the Group d’Etude des Lymphomes de l’Adulte (GELA); and a member of the société française de greffe de moelle (SFGM-TC). Martin GoreMartin GoreProfessor Martin Gore is the Medical Director of the Royal Marsden Hospital and Professor of Cancer Medicine at the Institute of Cancer Research. He qualified in medicine at St Bartholomew's Hospital, London and spent time in general practice before training in general internal medicine at University College Hospital, London. He joined the Ludwig Institute of Cancer Research in 1981 where he worked as a clinical scientist and was awarded a PhD for his work on breast cancer. Professor Gore serves on The Commission on Human Medicines, is the founder Co-Patron of the Rarer Cancers Foundation and was a founder Senior Investigator of the UK's National Institute for Health Research. He previously chaired the Department of Health's Gene Therapy Advisory Committee, is a past President of the UK Melanoma Study Group and a past Chair of the National Cancer Research Institute's Melanoma Clinical Studies Group. He has served on the Health and Safety Executive's Scientific Advisory Committee on Genetically Modified Organisms, the Council of the International Gynaecologic Cancer Society, the Programme Committee of the Annual Meeting of the American Society of Clinical Oncology and he was co-founder of the European International Kidney Cancer Symposium. He is a Medical Advisor to the US-based patient advocacy group the Kidney Cancer Association who awarded him the Eugene P. Schonfeld Memorial Lecturership in 2014, the first non-US recipient. He is the editor of the Gynaecological Cancer Section of Current Opinion in Oncology and has served on the editorial board of several journals including the Journal of Clinical Oncology. He has published over 500 articles and edited ten textbooks. Professor Gore's main research interests are the development of novel therapeutics in ovarian cancer, melanoma and renal cell carcinoma, particularly in the area of immunotherapy, gene therapy and targeted agents.

Moving Forward on Shifting Sands: Ethical Regulation of Gene Therapy Clinical Trials in the United Kingdom

The regulatory landscape for development and application of gene therapies worldwide is complex and surprisingly variable. This has been a source of considerable frustration to investigators in both academia and industry who are eager to bring novel therapies into the clinic. With this in mind, many countries are considering how to simplify the process while retaining good scientific and ethical oversight. The UK National Research Ethics Service (NRES) has recently taken the step of disestablishing its Gene Therapy Advisory Committee (GTAC). The reaction to this move has been somewhat mixed, so it is worth taking a closer look at its purpose and function as the gene and cell therapy community enters an era of increasing clinical activity and commercialization of products.

Editorial introductions

Current Opinion in Oncology was launched in 1989. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of psychiatry is divided into 15 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. Section Editors Bertrand Coiffier Bertrand Coiffier is Professor of Hematology at the Department of Hematology, Hospices Civils de Lyon and the University Claude Bernard, Lyon, France. After having specialized in hematology, Professor Coiffier has held a number of positions at the Hematology Department of the Edouard-Herriot Hospital, Lyon and then the Centre Hospitalier Lyon-Sud, Pierre-Benite. He is a member of several international societies, including the American Society of Hematology, the American Society of Clinical Oncology, the International Society for Medical Oncology, the European Haematology Association, and the European Society for Medical Oncology. Professor Coiffier is a founding member of the Group d’Etude des Lymphomes de l’Adulte (GELA) and has been President of the GELA since 2006. He has published over 300 papers in peer-reviewed journals. Anne-Sophie Michallet Anne-Sophie Michallet is a Doctor of Hematology at the Department of Hematology, Hospices Civils de Lyon and the University Claude Bernard, Lyon, France. After having specialized in hematology, she focused on lymphoproliferative disorders. She is a member of the French Group of Chronic Lymphocyic Leukemia (GFCLL and GOELAMS), the Group d’Etude des Lymphomes de l’Adulte (GELA); and a member of the société française de greffe de moelle (SFGM-TC). Ronald MitsuyasuRonald MitsuyasuDr Ronald Mitsuyasu is Professor of Medicine/Hematology-Oncology at the David Geffen School of Medicine at UCLA and the Director of the UCLA Center for Clinical AIDS Research and Education (CARE Center). Dr Mitsuyasu is Associate Director of the UCLA AIDS Institute and oversees its programs in Clinical Therapeutics and Biomedical Prevention. He is an established clinical investigator with over 25 years of experience in HIV clinical trials research and patient care. He established one of the first clinics for Kaposi's sarcoma and AIDS malignancies at UCLA in 1983. He is the Group Chair of the NCI-funded AIDS Malignancy Consortium (AMC) and is director of the State of California UCLA Collaborative Center for HIV/AIDS Research, which is known as the Network for AIDS Research in Los Angeles. Dr Mitsuyasu's research interests include clinical trial investigations of cytokines, immune-based therapies, biologic response modifiers, vaccines and gene therapies for HIV and treatments for AIDS-related malignancies. He has an extensive background in the use of cytokines, other biologic interventions, bone marrow and stem cell transplants and other novel therapies approaches for HIV. He has also pioneered the use of gene therapy for HIV infection. Martin GoreMartin GoreMartin Gore qualified in medicine at St Bartholomew's Hospital, London in 1974 and spent time in general practice before training in general internal medicine at University College Hospital, London. He joined the Ludwig Institute of Cancer Research in 1981 where he worked as a clinical scientist and was awarded a PhD for his work on breast cancer. Professor Gore joined the Royal Marsden Hospital training programme in 1984 and was appointed Consultant Cancer Physician at the Marsden and Senior Lecturer at the Institute of Cancer Research in 1988. His main research interests have been the development of novel therapeutics in ovarian cancer, melanoma and renal cell carcinoma particularly in the area of biologics, gene therapy and novel targeted agents. Professor Gore is Chairman of the UK Department of Health's Gene Therapy Advisory Committee and Vice-chairman of the Health and Safety Executive's Scientific Advisory Committee on Genetically Modified Organisms. He is currently Medical Director of the Royal Marsden Hospital in London. He is past President of the UK Melanoma Study Group and past Chair of the NCRI Melanoma Clinical Studies Group. He is on the Council of the International Gynaecologic Cancer Society. He is a member of the Gynaecologic Cancer Steering Committee of the NCI (US) and previously served on the Programme Committee of American Society of Clinical Oncology for the Gynecologic Cancer Track. He is also a Medical Advisor to the US Kidney Cancer Association. He is on the editorial board of several journals and has published over 300 articles and edited eight textbooks.

Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review

Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review

Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review

Human Gene TherapyVol. 20, No. 5 News and CommentsFuture Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) ReviewPublished Online:23 Oct 2009https://doi.org/10.1089/hum.2009.1538AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review*." , 20(5), p. 550FiguresReferencesRelatedDetails Volume 20Issue 5May 2009 InformationCopyright 2009, Mary Ann Liebert, Inc.To cite this article:Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review.Human Gene Therapy.May 2009.550-550.http://doi.org/10.1089/hum.2009.1538Published in Volume: 20 Issue 5: October 23, 2009PDF download

Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review

Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review

Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review

Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review

Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review

Human Gene TherapyVol. 19, No. 12 News and CommentsFuture Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) ReviewPublished Online:18 Dec 2008https://doi.org/10.1089/hum.2008.1217AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review." , 19(12), p. 1428FiguresReferencesRelatedDetails Volume 19Issue 12Dec 2008 InformationMary Ann Liebert, Inc.To cite this article:Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review.Human Gene Therapy.Dec 2008.1428-1428.http://doi.org/10.1089/hum.2008.1217Published in Volume: 19 Issue 12: December 18, 2008PDF download

Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review

Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review

Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review

Human Gene TherapyVol. 19, No. 9 GTAC MeetingsFuture Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) ReviewPublished Online:16 Sep 2008https://doi.org/10.1089/hum.2008.0916AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review." , 19(9), p. 966FiguresReferencesRelatedDetails Volume 19Issue 9Sep 2008 InformationMary Ann Liebert, Inc.To cite this article:Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review.Human Gene Therapy.Sep 2008.966-966.http://doi.org/10.1089/hum.2008.0916Published in Volume: 19 Issue 9: September 16, 2008PDF download

Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review

Human Gene TherapyVol. 19, No. 8 GTAC MeetingsFuture Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) ReviewPublished Online:28 Aug 2008https://doi.org/10.1089/hum.2008.0816AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review." , 19(8), p. 860FiguresReferencesRelatedDetails Volume 19Issue 8Aug 2008 InformationMary Ann Liebert, Inc.To cite this article:Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review.Human Gene Therapy.Aug 2008.860-860.http://doi.org/10.1089/hum.2008.0816Published in Volume: 19 Issue 8: August 28, 2008PDF download

Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review

Future Meeting Dates for UK Department of Health: Gene Therapy Advisory Committee (GTAC) Review

As Gelsinger Case Ends, Gene Therapy Suffers Another Blow

Five years after 18-year-old Jesse Gelsinger died in a gene therapy experiment, the U.S. Department of Justice has reached a settlement with the researchers and with their institutions. The department announced last week that the University of Pennsylvania (U. Penn) will pay fines of $517,496, and Children's National Medical Center in Washington, D.C., will pay $514,622. The settlement also restricts the clinical research of the three investigators. The Department of Justice alleged that toxic reactions in humans should have halted the trial earlier and that the lead investigators misrepresented clinical findings to the study's overseers, such as the National Institutes of Health (NIH) and the Food and Drug Administration (FDA). James Wilson of U. Penn, who had a financial interest in a company that stood to profit if the trial was successful, has agreed not to lead any FDA-regulated clinical trials for 5 years and be monitored for 3 years. Steven Raper of U. Penn and Mark Batshaw of Children's face less severe restrictions. Under the agreement, the scientists do not admit responsibility for Gelsinger's death. “Outrageous,” responds Gelsinger family attorney Alan Milstein, who said the family had hoped for a formal apology and the release of the clinical trial documents. While the Gelsinger case drew to a close, the field of gene therapy suffered another setback last month: A third child in a French trial for X-linked severe combined immunodeficiency (X-SCID) developed leukemia, French authorities reported on 24 January. Seventeen children have been successfully treated for SCID using gene therapy, making it the field's bright spot. But two patients in the French trial developed leukemia in late 2002 after a vector inserted near an oncogene; one child died last October. In response to the third leukemia case, the French trial has been halted again and FDA has suspended three U.S. SCID trials, but a trial in Britain continues. The two previous leukemia cases in France occurred in infants treated at 3 months of age or less, which led to speculation that cells with the oncogene insertion proliferate more readily in very young children. But the third child was treated at 9 months, suggesting that older children may also be at risk, says Harry Malech of NIH, who heads one of the U.S. trials. Experts expect to discuss the case when FDA's gene therapy advisory committee and NIH's Recombinant DNA Advisory Committee meet in March.

Treatment fillip for gene therapy ambitions

Treatment fillip for gene therapy ambitions

Immunomodulatory gene therapy for haematological malignancies.

Immunomodulatory gene therapy for haematological malignancies.

Preclinical safety testing of DISC-hGMCSF to support phase I clinical trials in cancer patients.

DISC-hGMCSF is a gH-deleted HSV-2 based vector expressing human GM-CSF that is being developed for cancer immunotherapy. To support first clinical use, a range of preclinical safety studies were performed using DISC-hGMCSF in addition to DISC-murine-GMCSF and the backbone vector, TA-HSV. The toxicity of the DISC vectors was assessed by repeated dose, neurovirulence and neuroinvasiveness studies in mice, and by safety studies in rabbits, guinea pigs and athymic nude mice. Studies were also conducted to determine whether the vector could establish latency in local ganglia in mice following intradermal injection, and whether it could reactivate from the latent state. The vector biodistribution following intravenous administration was also investigated in mice, using PCR to detect vector DNA. The DISC vectors were essentially non-toxic in all the systems studied. No adverse reactions were seen in mice receiving four intravenous doses of DISC-mGMCSF and the results from studies of neurovirulence, neuroinvasiveness, local tolerance in rabbit, general safety in mice and guinea pigs and safety in athymic nude mice were consistent with DISC being unable to replicate and cause disease. The vector could establish latency in local ganglia in mice, but at low efficiency, and could not reactivate infectious virions. Following intravenous administration, vector DNA was widely distributed up to Day 28, but by Day 56 had disappeared from gonads and brain and was only found in blood and liver. The panel of safety studies provided evidence that DISC-hGMCSF will be unable to replicate and cause disease, and has low toxicity in man. These data were presented to the Medicines Control Agency and the Gene Therapy Advisory Committee as part of the regulatory submissions for a clinical trial in melanoma patients. These submissions have been approved, and DISC-hGMCSF has now entered a phase I clinical trial in the UK by direct intratumoural injection.

Gene therapy advisory committee: long-term monitoring of patients participating in gene therapy: Health Departments of the United Kingdom.

Gene therapy advisory committee: long-term monitoring of patients participating in gene therapy: Health Departments of the United Kingdom.