cells) have shown that 10-20 million cells contain a broad repertoire of immune specificities 
(D.E. Mosier, personal communication; Bordignon, see letter). 
The patients will receive approximately six monthly infusions of autologous peripheral blood 
lymphocytes which have been transduced with the LASN vector. These Infusions will be given 
within a few days of gene introduction and before the cell population has had the opportunity to 
proliferate to a significant extent. We anticipate that from 1 to 100x10® cells/kg will be 
given with each infusion beginning with the cells obtained from 7 ml blood/Kg. This initial cell 
dose is about 1% the dose of cells given in TIL therapy. A comprehensive immunologic 
evaluation will be performed at the end of this series of infusions. (Section 8.2) The 
occurrence of any grade 3 or 4 toxicity associated with the cell infusion that is not easily 
reversed with medication will be a decision point in the protocol. The iv route of cell infusion 
will cease being used. The ip route will be instituted at this point. 
The child will have recently voided or the position of the bladder will be visualized by 
ultrasound. The skin of the abdominal midline will be prepared and draped following standard 
procedures for paracentesis. After administration of local anesthesia, an 18-22 gauge 
angiocath will be carefully inserted into the peritoneum at or adjacent to the midline below the 
umbilicus. (71) After the cell infusion is complete, the catheter will be removed and the 
patient observed closely for at least 1 hour. 
Adults receiving cellular immunotherapy with TIL for the treatment of malignant melanoma 
have been routinely given infusions of 2-4x10^ ^ cultured T cells (up to 6x10^/kg) and 1L2 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 SCID treated by bone marrow transplantation have been given up to 1 0® bone 
marrow cells/kg intravenously, usually without complications. Even though the initial cell 
infusions during parts 1 and 2 of this protocol involve small numbers of cells which are 
unlikely to cause untoward effects, these infusions will be carried out in the Pediatric-ICU to 
permit more Intensive monitoring of the patient’s response to the infusion. When sufficient 
experience has been gained with this protocol, the PI may elect to perform the cell infusions on 
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