Lymphocyte Gene Therapy for Mild Hunter Syndrome 
infusion into the patient is detailed in Appendix B. Several additional aspects of the protocol are 
described below. 
Transduced lymphocytes will be administered as soon as possible after gene introduction 
in culture. 
Each patient will receive 12, monthly infusions of autologous peripheral blood 
lymphocytes which have been transduced with the L2SN vector. The infusions will be given 
within 4 days of gene introduction and before the cell population has had the opportunity to 
proliferate to a significant extent. We anticipate that 5 x 10 7 cells (initial infusion) to 5 x 10 9 cells 
(maximum feasible) will be given with each infusion. 
For comparison, adults receiving cellular immunotherapy with TIL for the treatment of 
malignant melanoma have been routinely given infusions of 2 - 4 x 10 11 cultured T cells (up to 6 x 
10 9 /kg) and IL-2 in a single day. These adults have experienced symptoms ranging from no 
noticeable effects to various symptoms including chills, fever, lethargy, tachycardia, bradycardia, 
hypotension, shortness of breath, nausea, and vomiting. In most of these cases the symptoms are 
moderated by premedication and they are seldom severe. 
Children with MPS diseases treated by bone marrow transplantation have been given up to 
0. 5 x 10 9 marrow cells per kg body weight intravenously without major complications. 
Even though the initial (first and second) PBL infusions administered to each patient are 
small numbers of cells which are unlikely to cause adverse reactions, these infusions will be 
carried out an Intensive Care Unit at the University of Minnesota Hospital to permit close 
monitoring of the patient's response to the infusion. When sufficient experience has been gained 
with this protocol and each patient, the PI will decide to perform cell infusions at the Clinical 
Research Center of the University of Minnesota. 
This protocol is classified as research involving greater than minimal risk but presenting 
the prospect of direct benefit to the individual subject. Discomforts to the patient may include 
venipuncture and/or other modes of vascular access. The patient may experience chills, fever, 
tachycardia, nausea and vomiting, and/or shortness of breath during the cell infusion. Potential 
risks include cardiac arrhythmias, vascular thrombosis, pulmonary embolus, inadvertent infusion 
of contaminated cultures, or mislabeled cells. 
Potential risks with the gene insertion portion of the proposal include the inadvertent 
contamination of the retrovirus preparation with replication competent murine retrovirus 
generated by a recombination event occurring in the vector virus packaging cell line. During 
retroviral-media ted gene transfer, the cultured T-cells could also undergo an insertional event 
causing the malignant transformation of the cell. The cultured T-cell population could 
theoretically contain cell subpopulations with potential undesirable consequences for the patient 
such as autoreactive cells. Cancer patients treated with IL-2 infusions alone or with IL-2 plus 2-4 
x 10 n cultured expanded autologous T cells have experienced transient symptoms which may 
reflect immune phenomena such as joint aches (not arthritis) and skin rashes. Less than one-third 
of patients have experienced any symptoms and each has been associated with IL-2 treatment 
alone at a similar frequency so that the potential contribution by the T-cell infusions is unclear. 
Adverse drug reactions (ADRs) to the IND Drug will be reported promptly to the 
investigational Drug Branch (IDB), phone (301) 496-7957. ADR reports are required even if there 
is only a suspicion of a drug effect. A written report will follow within 10 working days. 
For each patient, the protocol will be concluded when the patient has received 12 infusions 
of transduced cells. Measurable clinical end-points will include increased leukocyte IDS enzyme 
levels, transduction frequency and urine glycosaminoglycan excretion and will be determined 
monthly. Physiologic evaluations will be performed at 3-month intervals. The study will require 
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