ISSN:1043-0342    

DOI:10.1089/hum.1990.1.4-371

出版商:Mary Ann Liebert, Inc.    

年代:1990

数据来源: MAL

摘要:

ABSTRACTPatients with malignant melanoma have been treated with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes (TIL) marked by retroviral gene transduction. The retroviral vector contained a gene coding for the bacterial enzyme neomycin phosphotransferase, such that transduced TIL expressing the enzyme could survive otherwise toxic concentrations of the neomycin analogue G418. For 1 patient, who exhibited a complete regression of cancer after treatment with TIL, lymphocytes from post-treatment blood and tumor biopsies were cultured in IL-2, and transduced TIL were recovered by G418 selection. Analysis of T-cell receptor heterogeneity indicated that the transduced TIL recovered from the tumor biopsy were different from TIL that were kept strictlyin vitroand selected in G418. The selection process required weeks in culture, during which time control cultures changed radically in subset composition, so there was also a simultaneous selection for long-termin vitrogrowth advantage. It cannot be certain that the TIL subsets preferentially recovered from the tumor biopsy corresponded to those that mediated complete elimination of tumor in this patient.

ISSN:1043-0342    

DOI:10.1089/hum.1990.1.4-373

出版商:Mary Ann Liebert, Inc.    

年代:1990

数据来源: MAL

摘要:

ABSTRACTFTO-2B rat hepatoma cells acquired mouse VL30 retrotransposon(s) when infected with Moloney murine leukemia virus (MoMLV) recombinant retroviruses produced from2 cells. The VL30 provirus was integrated into the rat genome, expressed at high levels, and its transcription induced 40-fold by dexamethasone. VL30 RNA was detected in hepatoma cells even without selection for the expression of the amino-3-glycosyl phosphotransferase (neo) gene, which was co-transferred with a MoMLV retrovirus. However, the extent of transfer of the VL30 RNA was inversely related to the titer of the MoMLV recombinant retrovirus. The restriction map analysis of the transferred VL30 provirus was identical to the mouse VL30s of the NVL subfamily which is known to be a significant fraction of the transcriptionally active VL30 subset. Additionally, the regenerating liver from an adult rat, which was infected with a defective MoMLV-derived retrovirus, expressed VL30 RNA. These results indicate that great care should be given to the transfer of unwanted passengers, like VL30, present in retroviral packaging cell lines like the2 cells, which are currently being used for gene therapy.

ISSN:1043-0342    

DOI:10.1089/hum.1990.1.4-385

出版商:Mary Ann Liebert, Inc.    

年代:1990

数据来源: MAL

摘要:

ABSTRACTLymphocytes can be readily transduced with retroviral vectors and the gene-modified lymphocytes will stably express the inserted genesin vitrofor long periods. As a prelude to studies in humans, we evaluated the survival of gene-modified T lymphocytes and the expression of the introduced genes in nonhuman primate T lymphocytes bothin vitroandin vivoto determine if lymphocytes could be a potential cellular gene therapy vehicle. Rhesus peripheral blood T-lymphocytes and/or lymph node lymphocytes were transduced with a retroviral vector that contained a bacterial neomycin resistance (NeoR) gene or both NeoR and the human adenosine deaminase (hADA) genes. The cells were then selected for NeoR expression by growth in the neomycin analogue G418 and the autologous gene-modified T cells were reintroduced into the donor animals. T lymphocytes were periodically regrown from the blood and selected in G418. Gene-modified cells persisted in 1 animal for 727 days as detected by analysis for vector DNA by polymerase chain reaction (PCR). Evidence for expression of the human ADA or NeoR genes has also been detected up to 727 days after cell infusion. These findings suggest that gene-modified T lymphocytes can survive and circulate for long periodsin vivoand can continue to express the introduced genes.

ISSN:1043-0342    

DOI:10.1089/hum.1990.1.4-399

出版商:Mary Ann Liebert, Inc.    

年代:1990

数据来源: MAL

摘要:

ABSTRACTConsideration of the ethics of human gene therapy does not seem to raise questions that have never been asked before. However, particularly when gene therapy is extended to modification of the germ cells, several ethical issues take on an added importance or significance. These issues are: (i) possible moral limitations on tampering withhuman nature; (ii) the extent of our responsibility to future generations; (iii) the appropriate use of early human embryos in genetic research. Furthermore, standard norms in clinical and research ethics require careful application to trials of human gene therapy, even if only somatic rather than germ-line improvements are sought.

ISSN:1043-0342    

DOI:10.1089/hum.1990.1.4-411

出版商:Mary Ann Liebert, Inc.    

年代:1990

数据来源: MAL

摘要:

ABSTRACTIt sometimes seems that genetic engineering is suspect, both to its practitioners and to the general public, because it is perceived as being somehow unnatural. This essay argues, on the basis of an analysis of two senses ofnatural,that there is nothing distinctively morally problematic about genetic engineering, at least on the grounds of its alleged unnaturalness. It does not follow that we cannot distinguish among morally legitimate and morally suspect uses of genetic engineering. But these distinctions can and should be drawn on the basis of the same considerations that enter into the evaluation of particular uses of any other medical procedure.

ISSN:1043-0342    

DOI:10.1089/hum.1990.1.4-419

出版商:Mary Ann Liebert, Inc.    

年代:1990

数据来源: MAL

摘要:

ABSTRACTIn this essay, I examine the sources and reach of the NIHPoints to Consider.These guidelines are based on normative considerations inherited from two sets of science policy deliberations that took place in the United States during the 1970s: the discussion of research with human subjects and the recombinant DNA debate. The combined lessons of those deliberations provide six criteria by which to evaluate human gene therapy proposals. While these criteria could be used to reject proposals to attempt germ-line gene therapy or enhancement engineering today, they provide no principled basis for publicly proscribing the development of these forms of genetic intervention. Instead, they will ultimately lead us to approach the moral limits of gene therapy as a professional policy question about the goals of medicine, rather than as a social policy question about the public good.

ISSN:1043-0342    

DOI:10.1089/hum.1990.1.4-425

出版商:Mary Ann Liebert, Inc.    

年代:1990

数据来源: MAL

ISSN:1043-0342    

DOI:10.1089/hum.1990.1.4-435

出版商:Mary Ann Liebert, Inc.    

年代:1990

数据来源: MAL

ISSN:1043-0342    

DOI:10.1089/hum.1990.1.4-441

出版商:Mary Ann Liebert, Inc.    

年代:1990

数据来源: MAL

ISSN:1043-0342    

DOI:10.1089/hum.1990.1.4-443

出版商:Mary Ann Liebert, Inc.    

年代:1990

数据来源: MAL