Recombinant DNA Advisory Committee - 12/2-3/93 
obtaining tumor specimens from patients whose primary tumor has already metastasized. 
Investigator Response-Dr. Sobol 
Dr. Sobol agreed to incorporate Ms. Meyers' suggestion about patient confidentiality into 
the Informed Consent document. In response to Dr. Leventhal's question about access 
to tumor specimens, Dr. Sobol stated that tumor cells will be obtained at the time of 
colon resection, even if the patient has metastatic disease. Those tumor specimens will 
be cryopreserved. Dr. Leventhal said that the Informed Consent document should be 
revised to include a statement that clearly explains that patients will have their primary 
tumors cryopreserved at the time of resection. Responding to questions about the in vivo 
data. Dr. Sobol said that 3 separate animal studies were performed. One experiment 
demonstrated an antitumor response effected by ID-2 transduced fibroblasts and noted 
that this response was not T cell-mediated. The second experiment demonstrated an 
antitumor response associated with a low level of IL-2 production; whereas, no antitumor 
response was observed at high levels of IL-2 production. A third experiment was 
conducted in which animals were first challenged with a live tumor transplant. Dr. 
Parkman explained that the animal studies are inconclusive regarding the optimum 
concentration of IL-2 for the proposed human study. Dr. Chase stated that although the 
protocol does not present any significant risk, there is no significant scientific conclusion 
derived from the preclinical studies that can be translated to the human study. Dr. 
Parkman noted that the investigators propose to treat colon cancer with the IL-2- 
producing cells, an aspect different from other previously approved protocols. Dr. Post 
added that animal experiments often are of limited value for human studies; therefore, 
the positive antitumor responses obtained from these studies should be considered. 
Dr. Sobol explained that if no toxicity is observed, 9 patients will be treated (3 patients 
in each of the 3 dose groups). If toxicity is observed, a larger number of patients will be 
required to define a safe dose. Dr. Straus suggested that accrual should be limited to a 
maximum of 12 patients. Dr. Sobol agreed to accept this upper limit of patient accrual. 
Dr. Sobol stated that a volume of between 100 and 200 milliliters (ml) of blood will be 
drawn at each immunization (i.e., a total of 400 to 800 ml over a two month period). 
Dr. Straus remarked that this volume of blood is higher than the allowable research 
limit. Dr. Sobol agreed to use the lower volume, 100 ml, of blood to be drawn at each 
immunization. Dr. Sobol agreed to revise the Informed Consent document and 
nontechnical abstract as suggested by the RAC. Regarding the lethal irradiation of cells, 
Dr. Sobol said that additional experiments are ongoing to determine the lethal dose of 
radiation. 
Committee Motion 
A motion was made by Dr. Parkman and seconded by Dr. Post to approve the protocol. 
RAC approval of the protocol is contingent on the review and approval of the following 
by the primary reviewers: (1) a revised Informed Consent document (incorporating the 
changes suggested by RAC members), (2) patient accrual will be limited to £ 12 patients, 
(3) data demonstrating lethal irradiation of tumor cells and fibroblasts, and (4) a revised 
Recombinant DNA Research, Volume 18 
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