       Document 0070
 DOCN  M9620070
 TI    Recent advances in the application of gene therapy to human disease.
 DT    9602
 AU    Hanania EG; Kavanagh J; Hortobagyi G; Giles RE; Champlin R; Deisseroth
       AB; Department of Hematology, University of Texas M.D. Anderson; Cancer
       Center, Houston, USA.
 SO    Am J Med. 1995 Nov;99(5):537-52. Unique Identifier : AIDSLINE
       MED/96066888
 AB    PURPOSE: To review the recent advances in the application of genetic
       modification strategies to the therapy of human diseases for which a
       molecular defect is known. METHODS: A computerized data bank search, the
       minutes of the National Institutes of Health (NIH) Recombinant DNA
       Advisory Committee published in the Federal Record, and reports of human
       clinical trials were used as data sources for this review. Clinical
       trials included in this review were published in the literature or
       approved by the NIH Recombinant DNA Advisory Committee. STUDY SELECTION:
       Evaluations of the efficacy of genetic modification strategies in
       clinical trials in human and in animal models are summarized. The design
       and outcome of the genetic modification strategies employed are reviewed
       for 16 marking trials, 16 gene replacement trials for molecular
       deficiency diseases, 3 chemoprotection and 4 chemotherapy sensitization
       trials, 11 cancer vaccine trials, 2 antisense oligonucleotide trials,
       and 3 molecular immunotherapy trials. DATA SYNTHESIS: The marking trials
       have shown that residual leukemia cells in the infused autologous marrow
       can contribute to relapse following autologous bone marrow transplants.
       The use of genetic modification for the replacement of missing or
       deficient genes in severe combined immunodeficiency, familial
       hypercholesterolemia, and cystic fibrosis has been associated with
       encouraging results so far. Clinical genetic therapy trials involving
       cancer vaccines, antisense oligonucleotides, adoptive immunotherapy with
       genetically modified T cells, delivery vectors containing interleukin-1
       receptor inhibitor for arthritis, replacement strategies for storage
       diseases, and genetic suppression of human immunodeficiency viral
       replication are just commencing. CONCLUSIONS: The clinical application
       of genetic modification techniques has thus far been successful in the
       beginning phases of this field. These early results suggest that
       continuation of gene therapy trials designed to correct the molecular
       changes that lead to disease states in humans is warranted. Evaluation
       of such clinical trials in the future may be based on the analysis of
       assays for short-term surrogate endpoints, as well as on the therapeutic
       outcomes of the trial, such as survival or remission.
 DE    Bone Marrow Transplantation  Clinical Trials  *Gene Therapy/METHODS
       Human  HIV Infections/THERAPY  Immunotherapy  Neoplasms/THERAPY
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Treatment Outcome
       JOURNAL ARTICLE  REVIEW  REVIEW, TUTORIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

