A dose of 5 x 10 6 cells will be administered initially. To allow time for development of an immune 
response, the second dose will be given on day 14; four subsequent doses will be given weekly and the 
patients observed for response. In responding patients, therapy with gene transfected cells will be 
repeated in courses consisting of 6 weekly injections at 1-2 month intervals. 
The initial treatment with transfected cancer cells will be given in the University of Miami’s Clinical 
Research Center. Patients will be hospitalized for 24 hours after administration to ensure careful 
monitoring for any unexpected side effects in a setting where third party payor reimbursement is not 
an issue. During the course of therapy, patients will undergo serial assessment of the clinical status of 
their disease status as defined below. 
In addition, peripheral blood samples will be obtained weekly for analysis of the mononuclear cell 
fraction for the presence of tumor specific T effector cells, by phenotypic and functional assays, in 
vitro studies for lymphocyte reactivity and lytic activity will be performed, using tumor cells as targets. 
Other reagent target cells will include K562 and Daudi for NK and LAK cells, the patient’s cancer cells 
cryopreserved from the initial biopsy (if available in adequate number), and the cancer cells from the 
established lines of the patient and other patients, to determine specificity for autologous and allogeneic 
targets. The patients’ cell lines pre- and post-transfection will be assayed for expression of HLA class 
I and II antigens to determine whether expression of these antigens correlates with immune 
responsiveness and whether gene transfection with 11-2 alters their expression. 
NOTE: We recognize that the irradiated tumor cells will only survive 7-10 days in vivo; the time 
course of their 11-2 production is therefore limited. The number of activated T effector cells may 
therefore be small and difficult to detect by the above studies because of the dilution in large numbers 
of unaltered circulating lymphocytes. Other laboratory projects at our center, however, intend to expand 
the number of these effector cells in vitro and to clone individual subsets of killer cells. The yield from 
these experiments will enhance our ability to assess changes in the patients’ immune reactivity to their 
own cancer cells. Moreover, the clonally expanded cells will be available as reagents for gene 
transfection studies. 
5.0 TOXICITY ASSESSMENT AND REPORTING 
The patients will be carefully evaluated over the first 24 hours after administration of the transfected 
cells, and then will be evaluated weekly until gene therapy terminates. Thereafter for study purposes, 
the patient will be followed monthly clinically to monitor disease status and survival. 
Patients will be observed for any side effects, which will be graded based on the Eastern 
Cooperative Oncology Group (ECOG) Toxicity Rating Scale, which grades toxicity as 0 (none), 1 
(mild), 2 (moderate), 3 (severe), 4 (life-threatening), and 5 (lethal). 
We do not expect significant side effects from this study because a relatively small volume of tumor 
cells will be administered, the tumor cells will not be replicating, only a short base sequence of viral 
(papilloma) replicase is utilized in our gene insertion technique, patients with active papilloma virus 
infection (warts) are excluded, and the amount of 11-2 produced locally by the subcutaneously 
administered transfected tumor cells is unlikely to have systemic effects. We will nevertheless monitor 
patients for the development of side effects that have been reported to occur after lymphokine 
administration, including the following: malaise; fever; nausea and/or vomiting; diarrhea; dyspnea; 
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