I DOSAGE AND ROUTE: 
Treatment 
Treatment 
Cohort 
Period I 
Period II 
0 
10*0 unmodified T-cells 
IV infusion x 1 
Same x 6 q 8 weeks 
i 
1 
10^ modified T-cells 
IV infusion x 1 
10*0 modified T-cells 
(or maximum safe dose) 
X 6 q 8 weeks 
1 
1 
2 
10^ modified T-cells 
IV infusion x 1 
II 
'1 
1 
3 
10*0 modified T-cells 
IV infusion x 1 
II 
PROCEDURE: T-lymphocytes from each seronegative twin will be obtained by lymphapheresis, 
separated into CD8+-enriched populations by monoclonal antibody binding 
techniques, activated by anti-CD3 and IL-2, and transduced using a retroviral 
vector. The introduced gene codes for a chimeric "universal receptor" which is 
HLA-unrestricted, recognizes the gpl20 moiety of the HIV envelope, and is able 
to induce cytolytic activity against HIV-infected T-cells. The transduced T-cells 
then undergo primary expansion ex vivo 10- to 1,000-fold over approximately 8- 
10 weeks and are frozen in aliquots for later serial infusions. These transduced T- 
cells will then, in preparation for infusion into the respective seropositive twin, be 
thawed and will undergo a secondary expansion over 2-3 weeks. 
In Treatment Period I, patients are randomized in a 1:3 ratio to receive a single IV 
infusion of unmodified lymphocytes (Cohort 0 comparison) or genetically 
modified lymphocytes from their respective twins. Dosage levels of genetically 
modified lymphocytes will be filled sequentially, starting with 10^ cells (Cohort 
1), 10^ cells (Cohort 2), and then lO^® cells (Cohort 3). Patients will be 
observed for safety variables; dose-limiting toxicity rates within each cohort will 
be assessed. All dosage cohorts will be filled before any patient advances into 
Period II. 
In Treatment Period II, the 18 patients who in Period I received genetically 
modified lymphocytes without dose-limiting toxicity (cohorts 1, 2, 3) may be 
given up to 6 additional infusions at the maximum cell dose that was deemed safe 
in Period I. Up to 12 new patients may in addition be treated accordingly, to a 
maximum total of 30. The 6 patients who received unmodified lymphocytes in 
Period I (cohort 0) may receive up to 6 additional infusions during Period II at the 
same dosage; up to 4 new patients may be entered to a maximum of 10 per 
cohort. Safety, primary disease status, and standard immunological parameters 
will be assessed, including survival of the uniquely marked T-cell populations. 
1 } 
Recombinant DNA Research, Volume 19 [131] 
