Publikationsdatum:
2000-04-28
Beschreibung:
Severe combined immunodeficiency-X1 (SCID-X1) is an X-linked inherited disorder characterized by an early block in T and natural killer (NK) lymphocyte differentiation. This block is caused by mutations of the gene encoding the gammac cytokine receptor subunit of interleukin-2, -4, -7, -9, and -15 receptors, which participates in the delivery of growth, survival, and differentiation signals to early lymphoid progenitors. After preclinical studies, a gene therapy trial for SCID-X1 was initiated, based on the use of complementary DNA containing a defective gammac Moloney retrovirus-derived vector and ex vivo infection of CD34+ cells. After a 10-month follow-up period, gammac transgene-expressing T and NK cells were detected in two patients. T, B, and NK cell counts and function, including antigen-specific responses, were comparable to those of age-matched controls. Thus, gene therapy was able to provide full correction of disease phenotype and, hence, clinical benefit.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cavazzana-Calvo, M -- Hacein-Bey, S -- de Saint Basile, G -- Gross, F -- Yvon, E -- Nusbaum, P -- Selz, F -- Hue, C -- Certain, S -- Casanova, J L -- Bousso, P -- Deist, F L -- Fischer, A -- New York, N.Y. -- Science. 2000 Apr 28;288(5466):669-72.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM Unit 429, Gene Therapy Laboratory, Cell Therapy Laboratory, Unite d'Immunologie et d'Hematologie Pediatriques, Hopital Necker, 75743 Paris Cedex 15, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10784449" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
Antigens, CD34/analysis
;
B-Lymphocytes/immunology
;
Gene Transfer Techniques
;
*Genetic Therapy
;
Genetic Vectors
;
Hematopoietic Stem Cell Transplantation
;
*Hematopoietic Stem Cells/cytology
;
Humans
;
Immunoglobulins/blood
;
Infant
;
Killer Cells, Natural/immunology
;
Lymphocyte Activation
;
Lymphocyte Count
;
Moloney murine leukemia virus/genetics
;
Mutation
;
Receptors, Antigen, T-Cell/analysis
;
Receptors, Interleukin/biosynthesis/*genetics
;
Severe Combined Immunodeficiency/genetics/*therapy
;
T-Lymphocyte Subsets/immunology
;
T-Lymphocytes/immunology
;
Transgenes
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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