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3 
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35 
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00 CO O 
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taU*M.UIi | >TU X. 
tUtrx «CSF m 
J. 
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lilt* ii(«L iill* imi. «• 
(yx CM -Of ntaM 
o 
0 
_j J 
11‘WrU H'inW. 
WUrrx CX-Cy 
fall* Wni Salt* ittL N. 
rUtyrt CM-CSf mh 
CT-2t BENCA CMS-S UwU Lmn 
(SxlO 1 dullest) (Sxll^dullcnjt) (lilO’diilUnae) OxlO s duJItfljc) 
Figure 4. Irradiated, GM-CSF secreting tumor cells stimulate increased 
systemic immunity relative to their non-transduced counterparts. Mice were 
inoculated with irradiated, non-transduced tumor cells or irradiated tumor 
cells secreting GM-CSF. Three weeks later, they were challenged with live 
wild-type tumor. o animals displaying growth of tumor challenge. • animals 
protected against tumor challenge. Model tumor lines: CT-26(colon ca) , 
RENCA(renal ca) ,CMS-5 (sarcoma) , Lewis Lung (lung ca). 
The therapeutic utility of GM-CSF transduced tumor cell vaccines to 
cause rejection of pre-established tumors was explored in several model 
systems in a similar manner. In each model system, the size of the tumor to 
be treated (the time of treatment after tumor inoculation) was an important 
determinant of the outcome. Tables 6 and 7 show data from representative 
experiments. The results in treating small sized pulmonary metastases (Table 
7) seems especially instructive to the clinicians who commonly encounter this 
in RCC patients. 
Table 6 
Treatment of mice bearing small pre-existing deposits of 
established tumor with GM-CSF gene transduced tumor cells 
Tumor System 
Number of Animals Tumor Free 100 days 
After Treatment 
B16 melanoma* 
Sxl04 tumor cells 
implanted 
1x105 tumor cells 
implanted 
No treatment control 1/5 
Irradiated wildtype 0/5 
Irradiated+GM-CSF gene 4/5 
0/5 
0/5 
2/5 
Renca RCC W 
5x103 tumor cells 
implanted 
1x104 tumor cells 
implanted 
No treatment control 0/10 
Irradiated wildtype 5/10 
Irradiated+GM-CSF 10/10 
1/10 
3/10 
9/10 
• For #w Bit turn or, C5TDU auec wen lrra«ed w ink I a 106 live wildtype, irradiated wikKypc, or irradiated CM-CSF (me 
tranad uccd ccJU 3 data aAer injection of fe live tumor. 
fc For (Sc tenet tumor. fUJk/c mice wtn treated with I a 106 
live wildtype, irradiated wtldtype, or irradiated 0M-C3F (me transduced tumor cell* i deyr tAcr injection of the live tumor. 
[298] 
Recombinant DNA Research, Volume 17 
