T-CELL MEDIATED REJECTION OF GENE-MODIFIED HIV-SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN HIV-INFECTED PATIENTS

The introduction and expression of genes in somatic cells is an innova tive therapy for correcting genetic deficiency diseases and augmenting immune function. A potential obstacle to gene therapy is the eliminat ion 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 vir us (HIV) receive CD8(+) HIV-specific cytotoxic T cells modified by ret roviral transduction to express a gene permitting positive and negativ e selection. However, five of six subjects developed cytotoxic T-lymph ocyte responses specific for the novel protein and eliminated the tran sduced cytotoxic T cells. The rejection of genetically modified cells by these immunocompromised hosts suggests that strategies to render ge ne-modified cells less susceptible to host immune surveillance will be required for successful gene therapy of immunocompetent hosts.