6.0 
Treatment Plan 
6.1 Location 
Patients will be treated at Sharp Memorial Hospital, San Diego, CA. 
6.2 Administration of Biological Agents 
Subjects will receive at least three subcutaneous immunizations at least two weeks apart with a 
mixture of irradiated autologous fibroblasts genetically modified to express the gene for IL-2 and 
irradiated autologous tumor cells. 
All subjects will be treated as outpatients. Vital signs will be checked prior to immunization. 
Subsequently, vital signs should be obtained qlh x 2. The patients should be examined qlh x 2 for 
inflammation at the injection site and for evidence of rash, wheezing or edema. Provided that there 
are no contraindications, subjects may be discharged 2 hours after drug administration. If discharge is 
contraindicated, patients will be followed in the hospital on a regular basis as deemed appropriate. 
7.0 Therapy Modification 
7.1 Dose Escalation 
In a single patient with glioblastoma treated with IL-2 secreting tumor cells or fibroblasts, transient 
erythema at immunization sites was not observed until the IL-2 dose exceeded 100 units/24 hrs. In 
our animal model, this dose of IL-2 was effective in generating systemic anti-tumor immunity (see 
Appendix 12.6). Hence, we plan to initiate therapy with transduced fibroblasts that secrete this dose 
of IL-2. Our data indicate that the transduced fibroblasts will express approximatley 200 to 400 
units of IL-2 per 10 6 cells per 24 hours. This will result in the administration of approximately 5 x 
10 5 transduced cells for the initial immunizations depending upon the level of IL-2 expression 
measured in vitro per 10 6 cells over 24 hours. We plan to escalate the dose of IL-2 secreting cells, as 
follows: 
Approximate Approximate # of 
Units of IL-2 Transduced Cells 
Cohort 1 100 5 x 10 5 
Cohort 2 200 1 x 10 6 
Cohort 3 400 2 x 10 6 
The transduced fibroblasts will be mixed with 1 x 10 7 unmodified irradiated tumor cells for 
immunization. The dose of transduced cells will be escalated when 3 patients at each dosage level 
have been treated and followed for 1 month without >_ grade 3 toxicity. Toxicity grades are listed in 
Appendix 12.1. If 3 patients at the same dosage level develop unacceptable treatment related toxicity 
(> grade 3 toxicity), the study will continue at the previous dose level until a total of 15 patients have 
been treated. 
Additional immunizations may be administered at approximately 2 week intervals, at the discretion of 
the investigators, as warranted by the demonstration of anti-tumor immune responses and 
improvement or stability in the patient's clinic status. 
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Recombinant DNA Research, Volume 18 
