Addition To: The Treatment of Patients with Advanced Cancer Using 
Cyclophosphamide, Interleukin-2 and Tumor Infiltrating 
Lymphocytes 
Project Number: 86-C-183 
Date of Approval: October 22, 1986 
Principal Investigator: Steven A. Rosenber^^^'oTT Ph.D., Chief 
of Surgery, NCI 
Associate Investigators (for this Addition) : 
R. Michael Blaese, M.D., Chief, Cellular Immunology Section, 
Metabolism Branch, NCI ’ 
(‘^^Kenneth Culver, M.D., Cellular Immunology Section, MB, NCI 
French Anderson, M.D., Chief, Laboratory of Molecular 
Hematology, NHLBI 
^^J-lCenneth Cometta, M.D., LMH, NHLBI 
Scott Freeman, M.D. , LMH, NHLBI 
I. OBJECTIVES 
1) To mark and follow the in vivo distribution and survival of tumor 
infiltrating lymphocytes (TIL) in order to gain knowledge that should assist in 
optimizing the use of autologous lymphocytes as immunotherapy vehicles. 
2) To evaluate the feasibility and safety of retroviral -mediated gene 
transfer using a marker gene in order to gain knowledge that should assist in 
augmenting TIL immunotherapy by the introduction of therapeutic genes. 
II. INTRODUCTION AND RATIONALE 
The Surgery Branch of the NCI has had extensive experience with the 
treatment of human cancer using cell transfer immunotherapy. In the Project to 
which this Addition is attached (86-C-183) a combination of chemotherapy and 
immunotherapy using interleukin-2 (IL-2) and autologous TIL for the treatment of 
advanced cancer has been underway since October 1986. A significant number of 
patients have shown beneficial clinical responses to this treatment and, 
therefore, optimization of the technique is a high priority. To aid in this 
optimization, more information is needed concerning the in vivo distribution and 
duration of survival of the reinfused TIL. Specifically, is there a correlation 
between clinical effectiveness and the continued presence of infused TIL: 
a) at the tiimor site? 
b) in adjacent lymph nodes or other reticuloendothelial sites? 
c) in the circulation? 
If so, are there characteristics that could distinguish a TIL that will be long- 
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Recombinant DNA Research, Volume 14 
