the regular patient care unit. 
This protocol is classified as research involving greater than miniinal 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. Local anesthesia and sedation may be 
required for the intraperitoneal infusions. 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. Intraperitoneal infusions could produce 
bowel perforation and subsequent serious peritoneal infection. 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 ceil line. During retroviral-mediated gene transfer 
the cultured T cells could also undergo an insertional event causing the malignant 
transformation of the cell (see section 1.5.5). The cultured T cell population could 
theoretically contain cell sub-populations with potential undesirable consequences for the 
patient such as autoreactive cells. Cancer patients treated with IL2 infusions alone or with IL2 
plus 2-4x10^ ^ 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 1/3 of patients have experienced any symptoms and each has been associated with IL2 
treatment alone at a similar frequency so that the potential contribution by the T cell infusions 
is unclear. 
The NeoR gene encodes for an enzyme (NPT-II) which inactivates the antibiotics Neomycin and 
Amikacin. NPT-ll does not inactivate other aminoglycoside antibiotics (such as Gentamicin and 
Tobramycin) and many other suitable alternatives for gram negative infections are available 
for clinical use. We have observed no untoward effects of expression of the NeoR gene in T cells 
either in vitro or in mice, monkeys, or humans who have received T cells expressing this 
enzyme. 
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. Previously unknown Grade 1 ,2 and 3 reactions will be reported to 
the NCI in writing using the “NCI Adverse Reactions Form for Investigational Agents" within 10 
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Recombinant DNA Research, Volume 14 
