Present: Professor Norman Nevin (Chair), Mrs Debbie Beirne, Professor Martin Gore, Professor Terry Hamblin, Dr Peter Harris, Mr Michael Harrison, Professor Jim Neil, Rev Dr Lee Rayfield, Dr Michael Waterhouse, Dr Adrian Lepper, Dr Richard Ashcroft, Professor Andrew Lever, Dr Caroline Benjamin, Professor Nick Lemoine (morning only), and Professor Alex Markham (morning only).

Observers: Dr Philip Harrison (MHRA) and Dr Mike Mackett (HSE).

Secretariat: Dr Jayne Spink, Dr Monika Preuss, and Mr Daniel Gooch.

Item 1: Introduction

The Chair welcomed two new GTAC Lay Members: Dr Adrian Lepper, a chartered engineer, and Dr Richard Ashcroft, a biomedical ethicist. The Chair also congratulated Prof Hamblin who had recently received the Binet-Rai Medal for outstanding contributions to Chronic Lymphoid Leukaemia research.

Item 2: Minutes of the 43rd meeting of GTAC

The minutes were agreed, without amendment, as an accurate and true record of the meeting.

Item 3: Matters Arising

The six letters sent out concerning correspondence arising from the last meeting were noted. The Secretariat also gave a short update on the Government's White Paper's four gene therapy commitments. In short:

• The cystic fibrosis £2.5 million bid was now closed; selected applicants were asked to submit full proposals;
  
• Safety research bid to close within days;
  
• How best to take forward the commitment regarding the £4 million for vector production was still under consideration;
  
• Full applications had been received for the £3 million for single gene disorders and would be sent out for review shortly .

Item 4: The Clinical Trials Directive

Earlier in the year, GTAC had submitted a written response to the Clinical Trials Directive Consultation, raising a number of points. The Committee was updated, and discussed, recent developments on this matter.

Item 5: SAE Update

The Secretariat had supplied the latest version of the database of SAEs and further details on SAEs received since the previous GTAC meeting in July 2003. The Committee had no further comments.

Item 6: Amendment: First Administration to Man of an Oncolytic Herpesvirus Vector Containing a Transgene for Granulocyte Macrophage Colony Stimulating Factor

Members were informed that an amendment to this study had been approved in September 2003 by Chairman's Action. There were no further comments.

Item 7: Protocol: First Administration of Dendritic Cells Transduced with ImmunoVEXtri-melan to Patients with Metastatic or Inoperable Melanoma, St George's Hospital, London

This is a phase I/II trial for the treatment of melanoma, which is a form of skin cancer. The approach to treating this disease is immunotherapy. The investigators propose to immunise patients with an anti-cancer vaccine which consists of melanoma-associated antigens. The carrier is a modified herpes simplex virus (HSV). It is an ex vivo study using dendritic cells from the blood of patients to stimulate T cells to mount an immune attack of melanoma cells.

The proposers joined the Committee to present the proposal to GTAC. Following their presentation, GTAC discussed the proposal and decided to approve the study, subject to minor amendments.

Item 8: Resubmitted protocol: A Phase I/II safety study of Met-Xia-OB83 in patients with pancreatic cancer, University of Liverpool (see also Item 4, Note of 43rd meeting)

This is a phase I/II trial in patients with advanced pancreatic cancer. Adenocarcinoma of the pancreas is a tumour that is difficult to diagnose because it is situated deep in the abdominal cavity. The study agent is a replication-disabled retrovirus. It contains the gene for cytochrome P450 which will be produced in these tumour cells. Cytochrome P450 is an enzyme which converts a pro-drug (cyclo-phosphamide) into an active toxic drug which is capable of killing cells. This strategy is called suicide therapy.

The proposers joined the Committee to present the proposal to GTAC. Following their presentation, GTAC decided to approve the study, subject to some minor amendments.

Item 9: Amendment: Phase I gene therapy protocol for X-linked chronic granulomatous disease, Great Ormond Street Hospital

Chronic granulomatous disease (CGD) is a group of rare, inherited disorders of the immune system that are caused by defects in the immune system. Affected patients, mainly boys, are vulnerable to severe recurrent bacterial and fungal infections and chronic inflammatory conditions.

In this amendment, the investigators asked for GTAC's permission to use a new, slightly amended, vector to introduce a functional copy of the affected gene. As before, it is a retroviral vector with the low affinity nerve growth factor receptor (LNGFR) marker gene removed. Members discussed the acceptability of the vector and changes to the PIL and background data which make mention of insertional mutagenesis seen in the French X-SCID trial. It was decided to approve the use of the vector under the GTAC approved protocol with some minor amendments to the patient information leaflet.

Item 10: Notifications

Two notifications were accepted by the Committee and recommended for review by the local REC.

Item 11: Chairman's actions

There were no comments on the 22 Chairman's actions taken since the last meeting.

Item 12: Any other business

GTAC's position on antisense technology.

The Secretariat had been approached with respect to GTAC's position on clinical trials using antisense technology. The Committee advised that in accordance with GTAC's guidance, the protocol must be reviewed by GTAC.

The definition of gene therapy, adopted by GTAC in 2000 is as follows: "The deliberate introduction of genetic material into human somatic cells for therapeutic, prophylactic or diagnostic purposes." The 7th Annual Report reads: "This definition was intended to include studies involving the use of most of the established techniques for delivering genes into cells. A non-exhaustive list of examples includes genetically modified viral vectors, liposome-encapsulated DNA, anti-sense techniques, naked DNA injection, DNA-mismatch repair, GM stem cell therapy, and xenotransplantation of animal cells (but not solid organs)." The ESGT's definition of gene therapy is: "Gene therapy is a technology by which genes or small DNA or RNA molecules are delivered to human cells, tissues or organs to correct a genetic defect, or to provide new therapeutic functions for the ultimate purpose of preventing or treating diseases."

Open meeting update Open Meeting (update)

The Secretariat's flyer for the Public Meeting was included with the papers. The Chairman thanked Mrs Fiona Sandford, Dr Richard Ashcroft and Mr Michael Harrison for agreeing to speak on the day (and to Chair in the case of Mr Harrison).

GMO regulations and gene therapy

The Secretariat had attended a meeting with MHRA, HSE and DEFRA in September. The aim of the meeting was to clarify roles and responsibilities in regulating gene therapy and to identify any gaps. It was agreed that it would be advantageous for guidance to be produced for circulation to all GM centres.

Correspondence

The Secretariat had received correspondence from a prospective patient volunteer and the sponsoring company in relation to the enrolment of that patient to a GTAC approved study. GTAC Members had been provided with the correspondence for information.

Meeting with CR-UK

The Secretariat, Department of Health and HSE representatives, Professor Lever and Mrs Debbie Beirne had a meeting with CR-UK (Birmingham) the previous Monday on the future of gene therapy in the context of the White Paper. Professor Lever, who chaired the meeting, updated GTAC about this meeting. Discussed had been two main areas: strategy on gene therapy service delivery and the White Paper commitment on gene therapy vector facilities.

Concluding remarks

The Secretariat offered to arrange media training for interested Members. The Secretariat looked forward to welcoming those members participating to the Edinburgh gene therapy conference and the GTAC public meeting.

The next committee meeting: Wednesday, 17 December at Skipton House.

GTAC Secretariat
November 2003

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