supernatant. Fibroblasts will be transduced with the retroviral vector 
supernatant and then washed extensively. They will be grown for several weeks 
In the absence of supernatant. The fibroblasts will then be washed extensively 
again prior to relnfuslon Into the patient. Taking into consideration that the 
half life of the retroviral vector in vitro Is 6 to 8 hours at 37 °C,and the 
extensive washing of cells, the propagation is unlikely to be contaminated 
with infectious retroviral particle in cells for injection. 
11.0 STATISTICAL CONSIDERATIONS 
11.1 Analysis of Peripheral Blood Specimens: 
Systemic IL-12, IFN-g, and IL-6 levels and the phenotype of circulating 
peripheral blood lymphocytes will be determined on days 0 (pre-vaccination), 
/, 14, 21, 28, 35 and 42. Follow-up multiple comparisons, based on either the 
paired- t or signed rank statistic, will be applied in the interpretation of 
significant results. 
11.2 Analysis of Local Toxicity: 
The incidence of severe, local reactions will be recorded. The 
relationship between local toxicity and the number of transferred cells and 
the amount of IL-12 elaborated per site per day will be determined. 
11.3 Clinical Response: 
The limited number of patients to be accrued (18) during the first phase 
of evaluation together with their varied histologies (3) will limit the 
generallzabili ty of the response rates that will be observed. Rates of 
response will be tabulated and compared to relevant norms. In the second phase 
of the evaluation, a total of 15 patients with each of these separate 
histologic tumor types (breast cancer, T-cell lymphoma, melanoma, and head and 
neck cancer) will be evaluated. 
12.0 ETHICAL CONSIDERATIONS 
Dr. Rosa Lynn Pinkus (Medical Ethics) will assist in developing and 
reviewing all protocol consent documents with the principal investigators. 
Every attempt will be made to protect the patients' and their family's 
privacy. Informed consent in this project is considered to be a process of 
shared decision-making between patient and physician. All written consents 
will be discussed with this concept in mind. 
13.0 RESPONSIBILITIES 
13.1 Consent- Drs . Tahara or Lotze. 
13.2 Harvest of the skin- Drs. Tahara or Lotze. 
13.3 Peritumoral injection of fibroblasts - Drs. Tahara or Lotze. 
13.4 Biopsy of vaccination sites- Drs. Tahara, Lotze, Rubin, Edington, or 
Salup or fellows under supervision. 
Recombinant DNA Research, Volume 19 
[661] 
