Recombinant DNA Advisory Committee - 06/7-8/93 
of antisense expressing cells for clinical use? 
Review-Ms. Meyers 
Ms. Meyers said that the section of the Informed Consent document that explains "sense" 
and "antisense" gene expression may not be understandable to lay persons. She 
suggested that the term "cures" should be changed to "treatments." 
Other Comments 
Dr. Parkman asked if the PI will select patients with gliomas that over-express IGF-1. 
What is the definition of over-expression? Does over-expression in tumor cells 
established in vitro correlate with primary tumors in vivo ? What is the transduction 
efficiency in human cells using liposome transfection? Does the rate of transduction 
correlate with therapeutic responses observed in animal studies? 
Dr. Post said that this proposal is very interesting; however, important human data is 
missing. Dr. Ilan responded that he had indicated in his written responses that the 
human data would be provided at the RAC meeting. Dr. Post stated that it is not an 
acceptable practice to allow Pis to withhold critical data until the meeting. 
Investigator Response-Dr. Ilan 
Dr. Ilan presented animal data that supported the basis for the proposed human trial. 
Rat C6 glioma cells express IGF-1 and form rapidly growing tumors in syngeneic 
animals. These cells lose tumorigenicity when transfected with the antisense IGF-1 
cDNA vector. Subcutaneous injection of transfected C6 cells into rats prevented tumor 
formation at the injection site and at distal sites. These anti-tumor effects result from a 
glioma-specific immune response involving CD8( + ) lymphocytes. Antisense blocking of 
IGF-1 expression may reverse a phenotype of the tumors that allows C6 glioma cells to 
evade the immune system. Modified C6 cells act as a vaccine against C6-induced 
tumors. Dr. Ilan presented additional data on other tumor types, such as osteosarcoma 
and rat teratocarcinoma. 
Drs. Miller and Geiduschek stated that although the animal data is encouraging, little 
information is known about the transduction of human cells. In response to Dr. 
Geiduschek's concern about the length of time required to grow a sufficient quantity of 
cells, Dr. Ilan explained that patients will receive radiation treatment for 2 months 
following surgery. During this time, tumor cells will be established in culture, 
transduced, and expanded to the necessary number of cells required for implantation. 
Dr. Ilan said that he is capable of reproducibly generating sufficient quantities of cells 
for treatment. Dr. Parkman inquired about the percentage of cells that are transduced. 
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Recombinant DNA Research, Volume 17 
