Recombinant DNA Advisory Committee - 06/7-8/93 
endpoints used to evaluate the trial were: (1) gene expression, (2) toxicity, and (3) 
antitumor response. In 4 of 5 patients, RNA expression of the injected DNA was 
detected by reverse transcriptase PCR on cells obtained at the site of injection. Protein 
expression was assayed by immunofluorescence and immunostaining techniques in 
several patients. Generally, there was no toxicity regarding renal, myocardial, liver, and 
hematological functions. The anti-DNA immune response did not increase following 
DNA-liposome treatment; therefore, the primary endpoint of the trial has been achieved. 
CTL responses to autologous tumor, particularly against human leukocyte antigen 
(HLA)-B7, were observed. In at least one patient, a melanoma nodule disappeared 85 
days following treatment. Several other tumor responses were observed; however, these 
responses could be non-specific. Dr. Nabel stated that he is encouraged by the 
augmented CTL responses to the injected gene product. 
Discussion 
Drs. Parkman and Miller expressed satisfaction in the initial trial. Dr. Nabel cautioned 
that only 1 patient demonstrated a significant antitumor response to the treatment. The 
new liposome preparation will allow delivery of 100-fold more DNA. Therefore, the 
proposed study may produce more efficacious results. Regarding the animal studies, the 
antitumor response appears to be dependent on the gene that is injected rather than the 
non-specific response to liposome-DNA complexes. In response to Dr. Carmen's 
question about IL-2, Dr. Nabel explained that patients will receive the IL-2 protein not 
the gene. 
Dr. Nabel explained the rationale for including other tumor types. Melanoma was 
chosen for the initial studies because noninvasive treatment was required. In the 
proposed protocol, other tumor types will be treated; 12 patients will be treated by direct 
intratumor injection and 12 patients by the catheter delivery method. The latter will be 
administered to patients with colon cancer, renal cell cancer, and metastatic melanoma. 
Renal and liver tumors with well accessible blood supplies are preferable targets for this 
therapy. Following a lengthy discussion about the types of tumor that should be 
approved for treatment, the RAC agreed not to place any restrictions on the tumor type. 
The committee members recommended that patients should have a good performance 
status in order to ensure the likelihood of successful treatment. 
Committee Motion 
A motion was made by Dr. Miller and seconded by Dr. Doi to approve this protocol 
contingent on submission of the following: (1) a revised patient eligibility section 
including the provision that patients who are eligible for catheter delivery of cationic 
liposomes must have a performance status of 0-1, and (2) a revised Informed Consent 
document that includes a recommendation that male/female patients use contraception 
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Recombinant DNA Research, Volume 17 
