INITIAL PROPOSAL OF CLINICAL RESEARCH PROJECT 
Date : 
.Clinical Project Number:. 
To: Chairman, Clinical Research Subpanel, NCI 
Recommended by: 
A- U< 
JC 
., Deputy Clinical Director, NCI 
-B ranch Chief (s) 
Title: IMMUNIZATION OF CANCER PATIENTS USING AUTOLOGOUS CANCER CELLS 
MODIFIED BY INSERTION OF THE GENE FOR TUMOR NECROSIS FACTOR 
Identifying Words: gene therapy, immunotherapy, interleukin-2, tumor infil- 
trating lymphocytes, tumor necrosis factor 
Principal Investigator: Steven A. Rosenberg, M.D., Ph 
1 
Associate Investigators: W.F. Anderson, M.D., Molecular Hematology ..Branch, NHLBI 
A.L. Asher, M.D., Surgery Branch, NCI^-^ ^ 
logy..J 
M.R. Blaese, Cellular Immunology Section; MB, NCI 
S.E. Ettinghausen, M.D., Surgery Branch, NCI 
P. Hwu, M.D., Surgery Branch, NCI 
A. Kasid, Ph.D., Surgery Branch, NCI ^ 
J.J. Mule, Ph.D., Surgery Branch, NCI fl* /'//(* 
D.R. Parkinson, M.D., Cancer Therapy Evaluation PrograW/^I 
D.J. Schwartzentruber , M.D., Surgery Branch, NCI f 
S.L. Topalian, M.D., Surgery Branch, NCI 
J.S. Weber, M.D., Surgery Branch, NCI 
J.R. Yannelli, Ph.D., Surgery Branch, NClM\ 
J.C. Yang, M.D., Surgery Branch, NCI 
W.M. Linehan, M.D., Surgery Branch, NOX J 
Estimated Duration of Study: 3 years 
Number and Kind of Subjects Needed: 
Number 
Sex 
(M or F) 
Age 
Patients 50 M&F 18 & older 
Precis: When tumor is resected from patients as part of the natural course 
of their treatment, an attempt will be made to establish a tissue culture 
line of the tumor. The gene coding for tumor necrosis factor will be 
introduced into these tumor cells and the integration and expression of this 
gene will be tested. Patients will become eligible for this study only if 
they develop metastatic cancer that has failed all standard effective 
treatment and have no other effective treatment options available to them. 
Tumor cells will be injected intradermally and subcutaneously into the thigh 
of these patients. The amount of tumor injected will be less than l/50th the total 
tumor burden of the patient. In previous studies we have shown that these gene- 
modified tumor cells are more immunogenic than the native unaltered tumor. 
Attempts will then be made to grow immune lymphocytes either from the tumor site 
Recombinant DNA Research, Volume 15 
[57] 
