Human Gene Therapy Subcommittee - 11/21-22/91 
should consider that they are not Phase I trials in the strictest sense. Traditional Phase I 
trials monitor the safety of the treatment, and the issue of efficacy is modest. In the 
setting of gene therapy, conventional standards that are used for drugs are not valid 
because efficacy is being considered in addition to toxicity. Dr. Leventhal agreed with 
Dr. Neiman and added that it is the efficacy of the gene transfer that is being 
considered, not the anti-tumor efficacy of the protocol. Dr. Parkman agreed and stated 
that the HGTS requires that the efficacy of gene transfer would be demonstrated in 
preclinical studies prior to submission of the protocol. 
Dr. Sobol continued his presentation of the protocol. This protocol is a Phase I study 
designed to determine safety, tumor response, and immune response to the proposed 
therapy. Patients will receive two immunizations, two weeks apart, of 10 7 irradiated 
tumor cells. These patients will also receive IL-2 transduced fibroblasts mixed with the 
tumor cells in a dose escalation manner. Fibroblasts will be injected that secrete 
between 20 and 120 units of IL-2. Preclinical data suggest that efficacy will be observed 
at a level of eight units of IL-2. Based on the current levels of IL-2 secretion that are 
produced with the current vector, these levels of IL-2 would translate into a range of 
between 1 x 10 6 and 1 x 10 7 fibroblasts. These are practical numbers of fibroblasts to 
grow and safely inject into patients. 
Dr. Sobol said that assays will be performed on peripheral blood cells to monitor the 
presence of the neo R gene as an indirect method of detecting any residual virus that may 
be capable of infecting other cell types in the patient. Humoral immunity assays will be 
performed on serum samples in addition to phenotyping. Dr. Leventhal inquired as to 
what was meant by humoral immunity studies. Dr. Sobol answered that they will 
perform assays to determine how patient serum samples react with the tumor cells; pre- 
and post-treatment serum samples will be compared. 
Dr. Parkman asked if the lesions or injection sites would be biopsied to determine 
persistence or duration of persistence of the IL-2 secreting fibroblast. Dr. Sobol replied 
that the human protocol does not include biopsy procedures; however, the investigators 
perform biopsies in the animal system. He added that the biopsy requirement may be 
too severe for patients. 
Dr. Sobol said that in the first few patients, peripheral blood mononuclear cells will be 
obtained and mixed with the patient's tumor extracts in an in vitro proliferation assay to 
determine cellular immunity. Patients will be followed for at least three months. If 
patients respond, these patients will be followed until those responses disappear. 
Dr. Leventhal asked the investigators what tumor types they are proposing to treat. Dr. 
Sobol said that they would like to keep the option available to treat all histologic types 
since it is difficult to predict in which types efficacy might be seen. Dr. Royston stated 
[280] 
Recombinant DNA Research, Volume 15 
