1.0 OBJECTIVES 
This is a phase I toxicity study in patients with advanced renal cell 
carcinoma (RCC) . The overall objective of this study is to evaluate a human 
tumor cell therapy with and without GM-CSF gene transduction for safety of 
clinical administration and induction of antitumor immune responses. In order 
to distinguish toxicities related to cell dose from potential toxicities due to 
expression of GM-CSF, two clinical dose escalation studies are contained in one 
trial. Escalating doses of lethally-irradiated, autologous renal cell carcinoma 
cells expanded in short-term culture and transduced with the human GM-CSF gene 
will be tested in one set of RCC patients to determine highest safely tolerated 
dose. Equivalent, escalating cell doses of expanded, irradiated, non-transduced 
RCC cells in another set of RCC patients will be evaluated for toxicities and 
determination of highest safely tolerated dose. Three primary objectives are: 
1. To evaluate the safety of skin injections of cultured, lethally- 
irradiated, autologous RCC cells as well as similarly prepared RCC 
cells transduced with the human GM-CSF gene secreting the cytokine 
at 24-48 ng/10 6 vaccine cells/24 hrs. 
2. To describe and quantitate the acute toxicities (including maximum 
tolerated dose if one is approached) and long-term toxicities of GM- 
CSF gene transduced cell therapy and to distinguish clinical 
toxicities related to cell dosage alone from those related to high 
levels of GM-CSF expression. 
3. To assay both in vitro and in vivo the contribution of RCC cell 
GM-CSF gene transduction to the induction of specific antitumor 
immune responses relative to irradiated non-transduced RCC vaccine 
cells. 
Two secondary objectives are: 
1. To seek preliminary evidence of therapeutic activity of injections 
of short-term cultured non-transduced irradiated autologous RCC cell 
injections. 
2. To seek preliminary evidence of therapeutic activity of GM-CSF gene 
transduced autologous irradiated RCC cell injections. 
Recombinant DNA Research, Volume 17 
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