T Lymphocyte-Directed Gene Therapy for ADA − SCID: Initial Trial Results After 4 Years

American Association for the Advancement of Science (AAAS) - Tập 270 Số 5235 - Trang 475-480 - 1995
R. Michael Blaese1, Kenneth W. Culver2, A. Dusty Miller3, Charles S. Carter4, Thomas A. Fleisher4, Mario Clerici2, Gene M. Shearer2, Lauren A. Chang5, Ya‐Wen Chiang6, Paul Tolstoshev6, Jay J. Greenblatt2, Steven A. Rosenberg2, Harvey G. Klein4, Madelyn Berger7, Craig A. Mullen1, W. Jay Ramsey1, Linda Muul8, Richard A. Morgan9, W. French Anderson5
1R. M. Blaese, C. A. Mullen, W. J. Ramsey, National Center for Human Genome Research, National Institutes of Health (NIH), Building 49, Room 2A03, Bethesda, MD 20892, USA, and National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA.
2K. W. Culver, M. Clerici, G. Shearer, J. J. Greenblatt, S. A. Rosenberg, NCI, NIH, Bethesda, MD 20892, USA.
3A. D. Miller, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
4C. S. Carter, T. Fleisher, H. Klein, Clinical Center, NIH, Bethesda, MD 20892, USA.
5L. Chang and W. F. Anderson, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD 20892, USA.
6Y. Chiang and P. Tolstoshev, Genetic Therapy, Gaithersburg, MD 20878, USA.
7M. Berger, Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
8L. Muul, National Center for Human Genome Research, NIH, Bethesda, MD 20892, USA.
9R. A. Morgan, National Center for Human Genome Research, NIH, Bethesda, MD 20892, USA, and NHLBI, NIH, Bethesda, MD 20892, USA.

Tóm tắt

In 1990, a clinical trial was started using retroviral-mediated transfer of the adenosine deaminase (ADA) gene into the T cells of two children with severe combined immunodeficiency (ADA − SCID). The number of blood T cells normalized as did many cellular and humoral immune responses. Gene treatment ended after 2 years, but integrated vector and ADA gene expression in T cells persisted. Although many components remain to be perfected, it is concluded here that gene therapy can be a safe and effective addition to treatment for some patients with this severe immunodeficiency disease.

Từ khóa


Tài liệu tham khảo

AKESON A.L., NORMAL AND MUTANT HUMAN ADENOSINE-DEAMINASE GENES, JOURNAL OF CELLULAR BIOCHEMISTRY 39, 217 (1989).

ARMENTANO D, EFFECT OF INTERNAL VIRAL SEQUENCES ON THE UTILITY OF RETROVIRAL VECTORS, JOURNAL OF VIROLOGY 61, 1647 (1987).

BIDDISON W.E., SELF DETERMINANTS RECOGNIZED BY HUMAN-VIRUS IMMUNE T-CELLS CAN BE DISTINGUISHED FROM THE SEROLOGICALLY DEFINED HLA ANTIGENS, JOURNAL OF IMMUNOLOGY 124, 548 (1980).

BLAESE R.M., HUM GENE THER 1, 327 (1990).

BLAESE R.M., PEDIATR RES: S49 (1993).

BLAESE R.M. unpublished data.

BUCKLEY R.H., J IMMUNOL 136, 398 (1986).

BUNNELL B.A., HIGH-EFFICIENCY RETROVIRAL-MEDIATED GENE-TRANSFER INTO HUMAN AND NONHUMAN PRIMATE PERIPHERAL-BLOOD LYMPHOCYTES, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 92, 7739 (1995).

CARSON D.A., THE POTENTIAL IMPORTANCE OF SOLUBLE DEOXYNUCLEOTIDASE ACTIVITY IN MEDIATING DEOXYADENOSINE TOXICITY IN HUMAN-LYMPHOBLASTS, JOURNAL OF IMMUNOLOGY 126, 348 (1981).

CARSON D.A., BIOCHEMICAL BASIS FOR THE ENHANCED TOXICITY OF DEOXYRIBONUCLEOSIDES TOWARD MALIGNANT HUMAN T-CELL LINES, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 76, 2430 (1979).

CHUN J.D., SUPPRESSION OF AN ANTIBODY TO ADENOSINE-DEAMINASE (ADA) IN AN ADA-DEFICIENT PATIENT RECEIVING POLYETHYLENE-GLYCOL MODIFIED ADENOSINE-DEAMINASE, ANNALS OF ALLERGY 70, 462 (1993).

CLERICI M, DETECTION OF 3 DISTINCT PATTERNS OF T-HELPER CELL DYSFUNCTION IN ASYMPTOMATIC, HUMAN IMMUNODEFICIENCY VIRUS-SEROPOSITIVE PATIENTS - INDEPENDENCE OF CD4+ CELL NUMBERS AND CLINICAL STAGING, JOURNAL OF CLINICAL INVESTIGATION 84, 1892 (1989).

CLERICI M, DETECTION OF CYTOTOXIC LYMPHOCYTES-T SPECIFIC FOR SYNTHETIC PEPTIDES OF GP160 IN HIV-SEROPOSITIVE INDIVIDUALS, JOURNAL OF IMMUNOLOGY 146, 2214 (1991).

COHEN A, DEOXYADENOSINE TRIPHOSPHATE AS A POTENTIALLY TOXIC METABOLITE IN ADENOSINE-DEAMINASE DEFICIENCY, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 75, 472 (1978).

COLEMAN M.S., IDENTIFICATION AND QUANTITATION OF ADENINE DEOXYNUCLEOTIDES IN ERYTHROCYTES OF A PATIENT WITH ADENOSINE-DEAMINASE DEFICIENCY AND SEVERE COMBINED IMMUNODEFICIENCY, JOURNAL OF BIOLOGICAL CHEMISTRY 253, 1619 (1978).

CULVER K, LYMPHOCYTES AS CELLULAR VEHICLES FOR GENE-THERAPY IN MOUSE AND MAN, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 88, 3155 (1991).

CULVER K.W., INVIVO EXPRESSION AND SURVIVAL OF GENE-MODIFIED LYMPHOCYTES-T IN RHESUS-MONKEYS, HUMAN GENE THERAPY 1, 399 (1990).

CULVER K.W., LYMPHOCYTE GENE-THERAPY, HUMAN GENE THERAPY 2, 107 (1991).

DADDONA P.E., GENETIC EXPRESSION IN PARTIAL ADENOSINE-DEAMINASE DEFICIENCY - MESSENGER-RNA LEVELS AND PROTEIN-TURNOVER FOR THE ENZYME VARIANTS IN HUMAN B-LYMPHOBLAST CELL-LINES, JOURNAL OF BIOLOGICAL CHEMISTRY 260, 3875 (1985).

DADDONA P.E., ADENOSINE-DEAMINASE DEFICIENCY WITH NORMAL IMMUNE FUNCTION - AN ACIDIC ENZYME MUTATION, JOURNAL OF CLINICAL INVESTIGATION 72, 483 (1983).

DAVIES E.G., EFFECT OF RED-CELL TRANSFUSIONS, THYMIC HORMONE AND DEOXYCYTIDINE IN SEVERE COMBINED IMMUNODEFICIENCY DUE TO ADENOSINE-DEAMINASE DEFICIENCY, CLINICAL AND EXPERIMENTAL IMMUNOLOGY 50, 303 (1982).

DONOFRIO J, OVERPRODUCTION OF ADENINE DEOXYNUCLEOSIDES AND DEOXYNUCLEOTIDES IN ADENOSINE-DEAMINASE DEFICIENCY WITH SEVERE COMBINED IMMUNODEFICIENCY DISEASE, JOURNAL OF CLINICAL INVESTIGATION 62, 884 (1978).

FERRARI G, AN INVIVO MODEL OF SOMATIC-CELL GENE-THERAPY FOR HUMAN SEVERE COMBINED IMMUNODEFICIENCY, SCIENCE 251, 1363 (1991).

FONG S.W., DEVELOPMENTAL PATTERNS OF ABO ISOAGGLUTININS IN NORMAL CHILDREN CORRELATED WITH EFFECTS OF AGE, SEX, AND MATERNAL ISOAGGLUTININS, TRANSFUSION 14, 551 (1974).

FRIEDRICH W, SEVERE COMBINED IMMUNODEFICIENCY - TREATMENT BY BONE-MARROW TRANSPLANTATION IN 15 INFANTS USING HLA-HAPLOIDENTICAL DONORS, EUROPEAN JOURNAL OF PEDIATRICS 144, 125 (1985).

FRIEDRICH W, IMMUNORECONSTITUTION IN SEVERE COMBINED IMMUNODEFICIENCY AFTER TRANSPLANTATION OF HLA-HAPLOIDENTICAL, T-CELL-DEPLETED BONE-MARROW, LANCET 1, 761 (1984).

GIBLETT E.R., ADENOSIN-DEAMINASE DEFICIENCY IN 2 PATIENTS WITH SEVERELY IMPAIRED CELLULAR IMMUNITY, LANCET 2, 1067 (1972).

GILBOA E, TRANSFER AND EXPRESSION OF CLONED GENES USING RETROVIRAL VECTORS, BIOTECHNIQUES 4, 504 (1986).

HERSHFIELD M.S., TREATMENT OF ADENOSINE-DEAMINASE DEFICIENCY WITH POLYETHYLENE-GLYCOL MODIFIED ADENOSINE-DEAMINASE, NEW ENGLAND JOURNAL OF MEDICINE 316, 589 (1987).

HERSHFIELD M.S., ENZYME REPLACEMENT THERAPY WITH POLYETHYLENE GLYCOL-ADENOSINE DEAMINASE IN ADENOSINE-DEAMINASE DEFICIENCY - OVERVIEW AND CASE-REPORTS OF 3 PATIENTS, INCLUDING 2 NOW RECEIVING GENE-THERAPY, PEDIATRIC RESEARCH 33, S42 (1993).

HERSHFIELD M.S., TREATMENT GENETIC DI 169, (1991).

HIRSCHHORN R, BIRTH DEFECTS-ORIG 19, 73 (1983).

HIRSCHHORN R, ERYTHROCYTE ADENOSINE-DEAMINASE DEFICIENCY WITHOUT IMMUNODEFICIENCY - EVIDENCE FOR AN UNSTABLE MUTANT ENZYME, JOURNAL OF CLINICAL INVESTIGATION 64, 1130 (1979).

HIRSCHHORN R, GENETIC-HETEROGENEITY IN PARTIAL ADENOSINE-DEAMINASE DEFICIENCY, JOURNAL OF CLINICAL INVESTIGATION 71, 1887 (1983).

HIRSCHHORN R, AMELIORATION OF NEUROLOGIC ABNORMALITIES AFTER ENZYME REPLACEMENT IN ADENOSINE-DEAMINASE DEFICIENCY, NEW ENGLAND JOURNAL OF MEDICINE 303, 377 (1980).

HOCK R.A., EXPRESSION OF HUMAN ADENOSINE-DEAMINASE FROM VARIOUS STRONG PROMOTERS AFTER GENE-TRANSFER INTO HUMAN HEMATOPOIETIC-CELL LINES, BLOOD 74, 876 (1989).

HUTTON J.J., BIOCHEMICAL AND FUNCTIONAL ABNORMALITIES IN LYMPHOCYTES FROM AN ADENOSINE DEAMINASE-DEFICIENT PATIENT DURING ENZYME REPLACEMENT THERAPY, JOURNAL OF CLINICAL INVESTIGATION 68, 413 (1981).

KANTOFF P.W., CORRECTION OF ADENOSINE-DEAMINASE DEFICIENCY IN CULTURED HUMAN T-CELLS AND B-CELLS BY RETROVIRUS-MEDIATED GENE-TRANSFER, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 83, 6563 (1986).

KEEVER C.A., TOLERANCE OF ENGRAFTED DONOR T-CELLS FOLLOWING BONE-MARROW TRANSPLANTATION FOR SEVERE COMBINED IMMUNODEFICIENCY, CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY 48, 261 (1988).

KIRCHNER H, POLYCLONAL IMMUNOGLOBULIN SECRETION BY HUMAN LYMPHOCYTES-B EXPOSED TO EPSTEIN-BARR VIRUS INVITRO, JOURNAL OF IMMUNOLOGY 122, 1310 (1979).

KOHN D.B., RETROVIRAL-MEDIATED GENE-TRANSFER INTO MAMMALIAN-CELLS, BLOOD CELLS 13, 285 (1987).

KOHN D.B., GENE-THERAPY FOR GENETIC-DISEASES, CANCER INVESTIGATION 7, 179 (1989).

KOHN D.B., ESTABLISHMENT AND CHARACTERIZATION OF ADENOSINE DEAMINASE-DEFICIENT HUMAN T-CELL LINES, JOURNAL OF IMMUNOLOGY 142, 3971 (1989).

KOHN D.B., ENGRAFTMENT OF GENE-MODIFIED UMBILICAL-CORD BLOOD-CELLS IN NEONATES WITH ADENOSINE-DEAMINASE DEFICIENCY, NATURE MEDICINE 1, 1017 (1995).

KOHN D.B., WISKOTT-ALDRICH SYNDROME (WAS) CARRIER DETECTION BY X-CHROMOSOME INACTIVATION ANALYSIS, PEDIATRIC RESEARCH 21, A313 (1987).

LEVY Y, ADENOSINE-DEAMINASE DEFICIENCY WITH LATE ONSET OF RECURRENT INFECTIONS RESPONSE TO TREATMENT WITH POLYETHYLENE-GLYCOL MODIFIED ADENOSINE-DEAMINASE, JOURNAL OF PEDIATRICS 113, 312 (1988).

MANN R, CONSTRUCTION OF A RETROVIRUS PACKAGING MUTANT AND ITS USE TO PRODUCE HELPER-FREE DEFECTIVE RETROVIRUS, CELL 33, 153 (1983).

MARKERT M.L., ADENOSINE-DEAMINASE AND PURINE NUCLEOSIDE PHOSPHORYLASE DEFICIENCIES - EVALUATION OF THERAPEUTIC INTERVENTIONS IN 8 PATIENTS, JOURNAL OF CLINICAL IMMUNOLOGY 7, 389 (1987).

MILLER A.D., IMPROVED RETROVIRAL VECTORS FOR GENE-TRANSFER AND EXPRESSION, BIOTECHNIQUES 7, 980 (1989).

MILLER A.D., REDESIGN OF RETROVIRUS PACKAGING CELL-LINES TO AVOID RECOMBINATION LEADING TO HELPER VIRUS PRODUCTION, MOLECULAR AND CELLULAR BIOLOGY 6, 2895 (1986).

MILLER A.D., A TRANSMISSIBLE RETROVIRUS EXPRESSING HUMAN HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE (HPRT) - GENE-TRANSFER INTO CELLS OBTAINED FROM HUMANS DEFICIENT IN HPRT, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES 80, 4709 (1983).

MORGAN R.A., APPLICATIONS OF THE POLYMERASE CHAIN-REACTION IN RETROVIRAL-MEDIATED GENE-TRANSFER AND THE ANALYSIS OF GENE-MARKED HUMAN TIL CELLS, HUMAN GENE THERAPY 1, 135 (1990).

MULLEN C.A. unpublished data.

OCHS H.D., ANTIBODY-RESPONSES TO BACTERIOPHAGE-PHI-X174 IN PATIENTS WITH ADENOSINE-DEAMINASE DEFICIENCY, BLOOD 80, 1163 (1992).

OREILLY R.J., IMMUNODEF REV 1, 273 (1989).

ORKIN S.H., MOLECULAR-CLONING OF HUMAN ADENOSINE-DEAMINASE GENE-SEQUENCES, JOURNAL OF BIOLOGICAL CHEMISTRY 258, 2753 (1983).

POLMAR S.H., ENZYME REPLACEMENT THERAPY FOR ADENOSINE-DEAMINASE DEFICIENCY AND SEVERE COMBINED IMMUNODEFICIENCY, NEW ENGLAND JOURNAL OF MEDICINE 295, 1337 (1976).

POLMAR S.H., METABOLIC ASPECTS OF IMMUNODEFICIENCY DISEASE, SEMINARS IN HEMATOLOGY 17, 30 (1980).

ROSENBERG S.A., GENE-TRANSFER INTO HUMANS - IMMUNOTHERAPY OF PATIENTS WITH ADVANCED MELANOMA, USING TUMOR-INFILTRATING LYMPHOCYTES MODIFIED BY RETROVIRAL GENE TRANSDUCTION, NEW ENGLAND JOURNAL OF MEDICINE 323, 570 (1990).

RUBINSTEIN A, INVIVO AND INVITRO EFFECTS OF THYMOSIN AND ADENOSINE-DEAMINASE ON ADENOSINE-DEAMINASE-DEFICIENT LYMPHOCYTES, NEW ENGLAND JOURNAL OF MEDICINE 300, 387 (1979).

SANTISTEBAN I, NOVEL SPLICING, MISSENSE, AND DELETION MUTATIONS IN 7 ADENOSINE-DEAMINASE DEFICIENT PATIENTS WITH LATE DELAYED-ONSET OF COMBINED IMMUNODEFICIENCY DISEASE - CONTRIBUTION OF GENOTYPE TO PHENOTYPE, JOURNAL OF CLINICAL INVESTIGATION 92, 2291 (1993).

SCHMALSTEIG F.C., LIMITED EFFECT OF ERYTHROCYTE AND PLASMA INFUSIONS IN ADENOSINE-DEAMINASE DEFICIENCY, JOURNAL OF PEDIATRICS 93, 597 (1978).

SHIMOTOHNO K, FORMATION OF INFECTIOUS PROGENY VIRUS AFTER INSERTION OF HERPES-SIMPLEX THYMIDINE KINASE GENE INTO DNA OF AN AVIAN RETROVIRUS, CELL 26, 67 (1981).

SILBER G.M., RECONSTITUTION OF T-CELL AND B-CELL FUNCTION AFTER LYMPHOCYTE-T-DEPLETED HAPLOIDENTICAL BONE-MARROW TRANSPLANTATION IN SEVERE COMBINED IMMUNODEFICIENCY DUE TO ADENOSINE-DEAMINASE DEFICIENCY, CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY 44, 317 (1987).

SORENSEN R.U., SELF LIMITED THROMBOCYTOPENIA IN A PATIENT TREATED WITH POLYETHYLENE-GLYCOL (PEG) MODIFIED ADENOSINE-DEAMINASE (ADA), PEDIATRIC RESEARCH 27, A162 (1990).

VALERIO D, ISOLATION OF CDNA CLONES FOR HUMAN ADENOSINE-DEAMINASE, GENE 25, 231 (1983).

WALDMANN T.A., ROLE OF SUPPRESSOR T-CELLS IN PATHOGENESIS OF COMMON VARIABLE HYPOGAMMAGLOBULINEMIA, LANCET 2, 609 (1974).

WALKER R.H., AABB TECHNICAL MANUA 622, (1993).

WATANABE S, ENCAPSIDATION SEQUENCES FOR SPLEEN NECROSIS VIRUS, AN AVIAN RETROVIRUS, ARE BETWEEN THE 5′ LONG TERMINAL REPEAT AND THE START OF THE GAG GENE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES 79, 5986 (1982).

WEINBERG K, T-LYMPHOCYTE ONTOGENY IN ADENOSINE-DEAMINASE DEFICIENT SEVERE COMBINED IMMUNE-DEFICIENCY AFTER TREATMENT WITH POLYETHYLENE-GLYCOL MODIFIED ADENOSINE-DEAMINASE, JOURNAL OF CLINICAL INVESTIGATION 92, 596 (1993).

WIGINTON D.A., CLONING OF CDNA SEQUENCES OF HUMAN ADENOSINE-DEAMINASE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES 80, 7481 (1983).

WIJNAENDTS L, DEVELOPMENT OF IMMUNOLOGICAL FUNCTIONS AFTER BONE-MARROW TRANSPLANTATION IN 33 PATIENTS WITH SEVERE COMBINED IMMUNODEFICIENCY, BLOOD 74, 2212 (1989).

WORTMANN R.L., BIOCHEMICAL BASIS FOR DIFFERENTIAL DEOXYADENOSINE TOXICITY TO LYMPHOBLAST-T AND LYMPHOBLAST-B - ROLE FOR 5′-NUCLEOTIDASE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 76, 2434 (1979).

YEAGER A.M., BONE-MARROW TRANSPLANTATION IN CHILDREN, PEDIATRIC ANNALS 17, 694 (1988).

ZIEGLER J.B., SEVERE COMBINED IMMUNODEFICIENCY AND ADENOSINE-DEAMINASE DEFICIENCY - FAILURE OF ENZYME REPLACEMENT THERAPY, ARCHIVES OF DISEASE IN CHILDHOOD 55, 452 (1980).

Thông tin
Thông tin xuất bản

American Association for the Advancement of Science (AAAS)

Tập 270 Số 5235

475-480

Thông tin tác giả