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Summary of results of clinical trials |
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| Target cells |
Vector |
Transgene |
Anti-HIV method |
Results |
|
|
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| CD8+ |
Retrovirus |
HyTk |
Introduction of suicide gene |
CTL response cleared modified cells [16]. |
| CD4+ |
Gold-particle-mediated |
Rev M10 |
Transdominant negative protein |
Detected Rev M10 until 2 months post infusion, preferential survival [36]. |
| CD4+ |
Retrovirus |
Rev M10 |
Transdominant negative protein |
Detected Rev M10 until 6 months post infusion, preferential survival [37]. |
| CD4+ |
Retrovirus |
TdRev and/or anti-sense TAR |
Transdominant negative proteins and anti-sense RNA |
Anti-HIV genes consistently detected for >100 weeks in six of six patients. Preferential survival of transduced cells during a period of high viral load in one patient [47]. |
| CD34+ |
Retrovirus |
TdRev |
Transdominant negative protein |
One patient died due to relapse to Hodgkin's disease. In second patient, detected vector in the progeny for >3 years, remission of leukemia and good viral load control achieved by administering HAART that cannot be attributed to gene therapy [38,39]. |
| CD34+ |
Retrovirus |
huM10 |
Transdominant negative protein |
huM10 could be detected in peripheral blood mononuclear cells (PBMC) for 1–3 months and then dropped to at or below the limit of detection over a two year follow-up period. Preferential survival of transduced cells during a period of high viral load in one patient [40]. |
| CD4+ |
Retrovirus |
CD4ζ |
Chimeric receptor |
Decrease of greater than 0.5 log mean in rectal tissue-associated HIV RNA for at least 14 days, detected CD4ζ in 1–3% of PBMCs at 8 weeks [42] |
| CD4+ |
Retrovirus |
CD4ζ |
Chimeric receptor |
Good expression of CD4ζ for at least 24 weeks in all patients; no difference between control and study group [43]. |
| CD4+ and CD8+ |
Retrovirus |
CD4ζ |
Chimeric receptor |
In 11 of 12 patients who received higher doses of modified CD8+ cells (109 or 1010), CD4ζ could be detected post-infusion for at least 15–40 weeks when they received additional infusions of modified cells. The group receiving IL-2 along with modified CD8+ cells showed a higher persistence of CD4ζ as compared to the group receiving no IL-2. In patients who received modified CD8+ and CD4+ cells, the cells were detected in the peripheral blood for at least 1 year post-infusion [41]. |
| CD34+ |
Retrovirus |
(RRE) decoy |
RNA decoy |
RRE-decoy-containing leukocytes could be isolated from peripheral blood even 1 year post-infusion but the numbers were extremely low [44]. |
| CD4+ |
Retrovirus |
RRz2 |
Ribozyme |
Over a 4 year period, PBMCs containing both RRz2 and LNL6 were consistently detected [46]. |
| CD34+ |
Retrovirus |
tat/vpr ribozyme |
Ribozyme |
Vector was detected in naïve T cells for >3 years; no correlation between changes in viremia or CD4+ T cell counts with vector expression or its detection in any cell type [45]. |
Marathe and Wooley Genetic Vaccines and Therapy 2007 5:5 doi:10.1186/1479-0556-5-5 |
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