T–cell mediated rejection of gene–modified HIV–specific cytotoxic T lymphocytes in HIV–infected patients
- 1 February 1996
- journal article
- clinical trial
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 2 (2), 216-223
- https://doi.org/10.1038/nm0296-216
Abstract
The introduction and expression of genes in somatic cells is an innovative therapy for correcting genetic deficiency diseases and augmenting immune function. A potential obstacle to gene therapy is the elimination of such gene-modified cells by an immune response to novel protein products of the introduced genes. We are conducting an immunotherapy trial in which individuals seropositive for human immunodeficiency virus (HIV) receive CD8+ HIV-specific cytotoxic T cells modified by retroviral transduction to express a gene permitting positive and negative selection. However, five of six subjects developed cytotoxic T-lymphocyte responses specific for the novel protein and eliminated the transduced cytotoxic T cells. The rejection of genetically modified cells by these immunocompromised hosts suggests that strategies to render gene-modified cells less susceptible to host immune surveillance will be required for successful gene therapy of immunocompetent hosts.Keywords
This publication has 51 references indexed in Scilit:
- Reconstitution of Cellular Immunity against Cytomegalovirus in Recipients of Allogeneic Bone Marrow by Transfer of T-Cell Clones from the DonorNew England Journal of Medicine, 1995
- Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics.The Journal of Experimental Medicine, 1995
- Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferationThe Lancet, 1995
- Principles for Adoptive T Cell Therapy of Human Viral DiseasesAnnual Review of Immunology, 1995
- Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosisNature Genetics, 1994
- Inactivation of E2a in recombinant adenoviruses improves the prospect for gene therapy in cystic fibrosisNature Genetics, 1994
- Gene marking to determine whether autologous marrow infusion restores long-term haemopoiesis in cancer patientsThe Lancet, 1993
- Gene-marking to trace origin of relapse after autologous bone-marrow transplantationThe Lancet, 1993
- Human gene therapy comes of ageNature, 1992
- Gene Transfer into Humans — Immunotherapy of Patients with Advanced Melanoma, Using Tumor-Infiltrating Lymphocytes Modified by Retroviral Gene TransductionNew England Journal of Medicine, 1990