アデノシンデアミナーゼ欠損症における遺伝子治療臨床研究

抄録

A 5 year-old boy with ADA deficiency has been treated with gene therapy which is the first trial in Japan since Augast 1995. T cells of patient's peripheral blood lymphocytes activated with anti-CD 3 antibody and recombinant IL-2 were transduced by a recombinant retrovirus vector, LASN, which contained cDNA of human ADA gene and then re-infused to the patient intravenously after 711 day-culture. We have already performed 10 cycles of the infusion without any side effects.
Concerning the transduction efficinecy of LASN in vitro, in situ PCR method showed 3-7% of ADAcDNA-positive cells after transduciton procedures. On the other hand, ADAcDNA has been detected in 10-20% of his peripheral blood lymphocytes by semi-quantitave PCR method. ADA enzyme activity in peripheral blood lymphocytes indreased progressively from below 1.0 units to 13.6 units during the therapy.
The count of his peripheral blood lymphocytes became to keep over 1,000/μl after the six in fusion. We have also found the improvement in both humoral and cellular immunological function tests such as specific antibody respones, serum immunoglobulin levels, isohemagglutinin titers, lymphocyte proliferation responses and DTH skin tests.
These results suggest definitely that genetically modified peripheral blood lymphocytes improve immune function in vivo after the repeated infusions. In addition to no major side effects we have never detected replication competent retrovirus in his peropheral blood during the course.