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Gene therapy takes further steps into the clinic
SCIENCE AND MEDICINE
Gene therapy takes further steps into the clinic neck cancers were so promising Introgen had asked the US FDA to fast-track approval of the therapy. Immune system manipulation attracted much attention at the meeting. Reiner Bolhuis (Academic Hospital, Rotterdam, Netherlands) described immunotherapy with cytotoxic lymphocytes engineered by use of technology created by meeting organiser Zelig Eshhar (Weizmann Institute of Science, Rehovot, Israel). “Eshhar has armed cytotoxic lymphocytes with a recognition structure that activates them when in contact with a unique target-cell marker”, said Bolhuis. Eshhar calls these engineered units “T-bodies”—chimeras of Improving European Union gene therapy the extracellular antigen Two European Commission concerted actions recognition domain of a were convened at the EWGT meeting: specific antibody and an • EGDR (European Gene Vector Database intracellular T-cell sigRepository), co-ordinated by Manuel Vega nalling domain. Bolhuis (Genethon), which will be a central source of reported a design based information, gene-therapy vectors and cell lines; on this chimera but con• EUREGENITHY, a user network co-ordinated by taining an extracellular TOdile Cohen-Haguenauer (Hôpital Saint Louis, cell receptor (TCR) Paris, France), which will survey and harmonise recognition domain national gene-therapy regulations and circulate directly attached to the information on regulation throughout the EU. or ␥ chain of the TCR.
he sixth meeting of the European Working Group on Human Gene Transfer and Therapy (EWGT) saw its rechristening as the European Society of Gene Therapy (ESGT), reflecting the move “from working hypotheses into clinical studies”, said EWGT president Olivier Danos (Genethon, Evry, France). Presentations at the meeting (Nov 21–24; Jerusalem, Israel) illustrated this move into the clinic. Abner Mhashilkar (Introgen, Austin, TX, USA), for example, explained that because phase I and II trials of p53 replacement therapy for non-smallcell lung carcinoma and head-and-
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Bolhuis hopes to start clinical trials of the TCR-engineered cytotoxic T cells in patients with renal carcinoma. Similar fused recognition units, said Eshhar, can be used to target viral vectors to specific cells. Keynote speaker Philip Greenberg (Fred Hutchinson Cancer Research Center, Seattle, WA, USA) reviewed clinical-trial data on adoptive T-celltherapy with antigen-specific T cells. For metastatic melanoma, his team has produced CD8 cells specific for melanocyte-specific antigens, which “home to tumour sites and eliminate all antigen-expressing tumour cells”. The group also has promising results from early clinical trials with T cells designed to attack HIV-infected cells. Israel’s first gene-therapy centre— the Goldyne Savad Gene Therapy Institute (Hadassah University Hospital, Jerusalem)—opened on Nov 22. The centre will “provide vectors . . . in a full GMP/GLP facility on a not-for-profit basis, pharmacogenomic screening, and tailor-made gene product generation for therapy”, said director Eithan Galun. Rachelle H B Fishman
Regular renal biopsies after transplantation help prevent rejection
M
onthly renal biopsy sampling for the first few months after renal transplantation, and giving corticosteroids for any inflammation detected, may decrease late acute and chronic renal rejection. Undetected, subclinical acute rejection of renal transplants occurs in 30% of patients in the first 3 months after transplantation. To test whether more aggressive treatment would improve outcomes,
76 patients were assigned to have biopsy samples taken 1, 2, 3, 6, and 12 months after transplantation, or at 6 and 12 months (controls). All patients were treated with corticosteroids if signs of rejection were found. In months 7–12, 33% of patients in the control group had acute rejection episodes but only 11% from the biopsy group. After 2 years, graft survival was 97% in the biopsy group and 83% in the control
group (J Am Soc Nephrol 1998; 9: 2129–34). “The conclusions are tentative because of the small numbers”, says author David Rush (University of Manitoba, Winnipeg, Canada). “We would also love to have a test that can pick up silent [subclinical] rejection of the graft that does not involve an invasive method.” Hannah Wunsch
Cosmetically, tissue adhesives are as good as sutures for closing wounds hich is best for closing wounds: octylcyanoacrylate tissue adhesive or traditional monofilament sutures? One of the most important criteria used to compare these methods, apart from comfort, has been cosmetic outcome. A new study confirms that long-term cosmetic outcome of lacerations closed with tissue adhesives equals that of suture repair. 135 patients with 136 wounds attending the emergency department of Ottawa General Hospital, Canada, were followed for up to 1 year after their injury. Experts, who were
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unaware of the method of wound closure, examined the lacerations 5–10 days, 3 months, and, in the case of 77 patients, 1 year after injury. At 1 year, 73% of wounds closed with glue scored the maximum cosmesis score. 68% of sutured wounds achieved the same score. On a visual analogue cosmesis score both groups scored 69 (Ann Emerg Med 1998; 32: 645–49). The 1-year results were consistent with 3-month outcomes, and the authors write that 80% of the skin’s original tensile strength has been regained by
3 months after skin closure, “so it is unlikely that significant changes in wound remodelling or scar widening would occur between 3 months and 1 year that would change the cosmetic outcome”. But, adds co-author Mario Jarnmuske, “although scores at 3 months have served as a fairly accurate early indicator of cosmetic outcome, 12-month scores are more accurate, since we must look at scar maturation to make a definitive statement about glues”. Angela Pirisi
THE LANCET • Vol 352 • December 5, 1998
Gene therapy takes further steps into the clinic neck cancers were so promising Introgen had asked the US FDA to fast-track approval of the therapy. Immune system manipulation attracted much attention at the meeting. Reiner Bolhuis (Academic Hospital, Rotterdam, Netherlands) described immunotherapy with cytotoxic lymphocytes engineered by use of technology created by meeting organiser Zelig Eshhar (Weizmann Institute of Science, Rehovot, Israel). “Eshhar has armed cytotoxic lymphocytes with a recognition structure that activates them when in contact with a unique target-cell marker”, said Bolhuis. Eshhar calls these engineered units “T-bodies”—chimeras of Improving European Union gene therapy the extracellular antigen Two European Commission concerted actions recognition domain of a were convened at the EWGT meeting: specific antibody and an • EGDR (European Gene Vector Database intracellular T-cell sigRepository), co-ordinated by Manuel Vega nalling domain. Bolhuis (Genethon), which will be a central source of reported a design based information, gene-therapy vectors and cell lines; on this chimera but con• EUREGENITHY, a user network co-ordinated by taining an extracellular TOdile Cohen-Haguenauer (Hôpital Saint Louis, cell receptor (TCR) Paris, France), which will survey and harmonise recognition domain national gene-therapy regulations and circulate directly attached to the information on regulation throughout the EU. or ␥ chain of the TCR.
he sixth meeting of the European Working Group on Human Gene Transfer and Therapy (EWGT) saw its rechristening as the European Society of Gene Therapy (ESGT), reflecting the move “from working hypotheses into clinical studies”, said EWGT president Olivier Danos (Genethon, Evry, France). Presentations at the meeting (Nov 21–24; Jerusalem, Israel) illustrated this move into the clinic. Abner Mhashilkar (Introgen, Austin, TX, USA), for example, explained that because phase I and II trials of p53 replacement therapy for non-smallcell lung carcinoma and head-and-
T
Bolhuis hopes to start clinical trials of the TCR-engineered cytotoxic T cells in patients with renal carcinoma. Similar fused recognition units, said Eshhar, can be used to target viral vectors to specific cells. Keynote speaker Philip Greenberg (Fred Hutchinson Cancer Research Center, Seattle, WA, USA) reviewed clinical-trial data on adoptive T-celltherapy with antigen-specific T cells. For metastatic melanoma, his team has produced CD8 cells specific for melanocyte-specific antigens, which “home to tumour sites and eliminate all antigen-expressing tumour cells”. The group also has promising results from early clinical trials with T cells designed to attack HIV-infected cells. Israel’s first gene-therapy centre— the Goldyne Savad Gene Therapy Institute (Hadassah University Hospital, Jerusalem)—opened on Nov 22. The centre will “provide vectors . . . in a full GMP/GLP facility on a not-for-profit basis, pharmacogenomic screening, and tailor-made gene product generation for therapy”, said director Eithan Galun. Rachelle H B Fishman
Regular renal biopsies after transplantation help prevent rejection
M
onthly renal biopsy sampling for the first few months after renal transplantation, and giving corticosteroids for any inflammation detected, may decrease late acute and chronic renal rejection. Undetected, subclinical acute rejection of renal transplants occurs in 30% of patients in the first 3 months after transplantation. To test whether more aggressive treatment would improve outcomes,
76 patients were assigned to have biopsy samples taken 1, 2, 3, 6, and 12 months after transplantation, or at 6 and 12 months (controls). All patients were treated with corticosteroids if signs of rejection were found. In months 7–12, 33% of patients in the control group had acute rejection episodes but only 11% from the biopsy group. After 2 years, graft survival was 97% in the biopsy group and 83% in the control
group (J Am Soc Nephrol 1998; 9: 2129–34). “The conclusions are tentative because of the small numbers”, says author David Rush (University of Manitoba, Winnipeg, Canada). “We would also love to have a test that can pick up silent [subclinical] rejection of the graft that does not involve an invasive method.” Hannah Wunsch
Cosmetically, tissue adhesives are as good as sutures for closing wounds hich is best for closing wounds: octylcyanoacrylate tissue adhesive or traditional monofilament sutures? One of the most important criteria used to compare these methods, apart from comfort, has been cosmetic outcome. A new study confirms that long-term cosmetic outcome of lacerations closed with tissue adhesives equals that of suture repair. 135 patients with 136 wounds attending the emergency department of Ottawa General Hospital, Canada, were followed for up to 1 year after their injury. Experts, who were
W
1834
unaware of the method of wound closure, examined the lacerations 5–10 days, 3 months, and, in the case of 77 patients, 1 year after injury. At 1 year, 73% of wounds closed with glue scored the maximum cosmesis score. 68% of sutured wounds achieved the same score. On a visual analogue cosmesis score both groups scored 69 (Ann Emerg Med 1998; 32: 645–49). The 1-year results were consistent with 3-month outcomes, and the authors write that 80% of the skin’s original tensile strength has been regained by
3 months after skin closure, “so it is unlikely that significant changes in wound remodelling or scar widening would occur between 3 months and 1 year that would change the cosmetic outcome”. But, adds co-author Mario Jarnmuske, “although scores at 3 months have served as a fairly accurate early indicator of cosmetic outcome, 12-month scores are more accurate, since we must look at scar maturation to make a definitive statement about glues”. Angela Pirisi
THE LANCET • Vol 352 • December 5, 1998