News News cer cells will render them susceptible to the antiviral drug gancyclovir. Irradiated ovarian cancer cells with the added gene will be injected into the peritoneum to deliver the gene to the ovarian tumor. Gancyclovir will thus be expected to kill the cancer cells receiving the gene.
—ByJMWaalen
Gene Therapy for ADA Takes Next Step The Recombinant DNA Advisory Committee has approved an amended gene therapy protocol for two children who have already benefited from their pioneering gene treatments for an extremely rare, inherited immune system disorder, adenosine deaminase (ADA) deficiency. "We are exceptionally pleased with our patients' progress so far," Michael Blaese, M.D., of the National Cancer Institute, told members of the RAC, citing significant improvements in lymphocyte counts and immune responses since (he initial gene therapy studies began in 1990 and 1991. However, supplemental therapy is needed, Blaese said, because there are still "holes" in the children's immune repertoire that leave them vulnerable to potentially life-threatening infections. According to both Blaese and W. French Anderson, M.D., of the National Heart, Lung, and Blood Institute, the amended gene therapy protocol is designed to plug up these holes by inserting a healthy ADA gene into a population of blood stem cells, which are far more primitive than the T cells now being used, and from which, in theory, the missing ADA enzyme would be churned out indefinitely. By adding a gene to these early stem cells (CD 34+ cells) - the parent cells of T lymphocytes - "the benefit could be profound," Anderson said. "Basically, we're talking about a cure... on the basis of a minute risk." Some RAC members were not convinced. Although the proposed study won approval by an 1 l-to-3 margin (with 2 abstentions), several RAC members felt the use of a new target cell system as well as a new retroviral vector went far beyond the original protocol, and required a review from scratch. Others were concerned about the proposed treatment's anticipated efficacy, given the lack of a good animal model for ADA, and the safety risks associated with an increasing number of potentially mutagenic events. Finally, there were ethical reservations about simultaneously initiating a second gene therapy protocol in children who are reportedly "doing so well" on their present therapy. Anderson told the RAC that no matter how well the children are doing, there is uncertainty about how long their immunologic protection may last, and the investigators see stem cell therapy as the best hope for a normal life. But Anderson stressed the protocol would not be limited solely to these patients and will be made available to other ADA children "as they come along." —By Susan Jenks
382
Researchers Struggle To Get Fetal Tissue For Cancer Research While the federal ban on the use of fetal tissue from induced abortions in human therapeutic transplants continues, cancer researchers are using fetal tissue in laboratory systems to study oncogenes, cancer formation, and immune system development. Many are uncomfortable talking about their work with fetal tissue because of misconceptions about the extent of the ban. Some say they could not do their research without it. Others have developed alternative systems, rather than deal with difficulties in obtaining fetal tissue and the stigma surrounding its use. 'This research is continuing because it's important," although some people are mistakenly concerned that it's not allowable, according to Faye Austin, Ph.D., associate director for the extramural research program in NCI's Division of Cancer Biology, Diagnosis, and Centers. "Many don't understand that the ban is just on transplantation [of fetal tissue] to patients for therapeutic purposes," Austin said. "The ban is very restricted." Since the ban, many NCI grantees have stopped using fetal tissue or significantly dropped the percentage of their grants that cover fetal tissue work, according to Harry Canter, chief of NCI's Research Analysis Evaluation Branch.
Access Not Easy "We have extraordinary trouble getting [fetal tissue]," said Dennis J. Slamon, M.D., Ph.D., associate professor of medicine at the University of California at Los Angeles. He uses tissue collected 5 or 6 years ago, before the ban. Slamon is using fetal tissue to study oncogenes and tumor suppressor genes.
Journal of the National Cancer Institute
Downloaded from http://jnci.oxfordjournals.org/ at Université Laval on July 13, 2015
and the plasmid incorporated into the cell's genome, ultimately resulting in expression of HLA-B7. In perhaps the most exotic gene therapy trial approved by the RAC to date, Scott Freeman, M.D., and colleagues at the University of Rochester have devised a protocol for ovarian cancer in which a gene added to ovarian can-
—ByJMWaalen
Gene Therapy for ADA Takes Next Step The Recombinant DNA Advisory Committee has approved an amended gene therapy protocol for two children who have already benefited from their pioneering gene treatments for an extremely rare, inherited immune system disorder, adenosine deaminase (ADA) deficiency. "We are exceptionally pleased with our patients' progress so far," Michael Blaese, M.D., of the National Cancer Institute, told members of the RAC, citing significant improvements in lymphocyte counts and immune responses since (he initial gene therapy studies began in 1990 and 1991. However, supplemental therapy is needed, Blaese said, because there are still "holes" in the children's immune repertoire that leave them vulnerable to potentially life-threatening infections. According to both Blaese and W. French Anderson, M.D., of the National Heart, Lung, and Blood Institute, the amended gene therapy protocol is designed to plug up these holes by inserting a healthy ADA gene into a population of blood stem cells, which are far more primitive than the T cells now being used, and from which, in theory, the missing ADA enzyme would be churned out indefinitely. By adding a gene to these early stem cells (CD 34+ cells) - the parent cells of T lymphocytes - "the benefit could be profound," Anderson said. "Basically, we're talking about a cure... on the basis of a minute risk." Some RAC members were not convinced. Although the proposed study won approval by an 1 l-to-3 margin (with 2 abstentions), several RAC members felt the use of a new target cell system as well as a new retroviral vector went far beyond the original protocol, and required a review from scratch. Others were concerned about the proposed treatment's anticipated efficacy, given the lack of a good animal model for ADA, and the safety risks associated with an increasing number of potentially mutagenic events. Finally, there were ethical reservations about simultaneously initiating a second gene therapy protocol in children who are reportedly "doing so well" on their present therapy. Anderson told the RAC that no matter how well the children are doing, there is uncertainty about how long their immunologic protection may last, and the investigators see stem cell therapy as the best hope for a normal life. But Anderson stressed the protocol would not be limited solely to these patients and will be made available to other ADA children "as they come along." —By Susan Jenks
382
Researchers Struggle To Get Fetal Tissue For Cancer Research While the federal ban on the use of fetal tissue from induced abortions in human therapeutic transplants continues, cancer researchers are using fetal tissue in laboratory systems to study oncogenes, cancer formation, and immune system development. Many are uncomfortable talking about their work with fetal tissue because of misconceptions about the extent of the ban. Some say they could not do their research without it. Others have developed alternative systems, rather than deal with difficulties in obtaining fetal tissue and the stigma surrounding its use. 'This research is continuing because it's important," although some people are mistakenly concerned that it's not allowable, according to Faye Austin, Ph.D., associate director for the extramural research program in NCI's Division of Cancer Biology, Diagnosis, and Centers. "Many don't understand that the ban is just on transplantation [of fetal tissue] to patients for therapeutic purposes," Austin said. "The ban is very restricted." Since the ban, many NCI grantees have stopped using fetal tissue or significantly dropped the percentage of their grants that cover fetal tissue work, according to Harry Canter, chief of NCI's Research Analysis Evaluation Branch.
Access Not Easy "We have extraordinary trouble getting [fetal tissue]," said Dennis J. Slamon, M.D., Ph.D., associate professor of medicine at the University of California at Los Angeles. He uses tissue collected 5 or 6 years ago, before the ban. Slamon is using fetal tissue to study oncogenes and tumor suppressor genes.
Journal of the National Cancer Institute
Downloaded from http://jnci.oxfordjournals.org/ at Université Laval on July 13, 2015
and the plasmid incorporated into the cell's genome, ultimately resulting in expression of HLA-B7. In perhaps the most exotic gene therapy trial approved by the RAC to date, Scott Freeman, M.D., and colleagues at the University of Rochester have devised a protocol for ovarian cancer in which a gene added to ovarian can-
