OCT-28-94 09.06 FROM . USC DIV. HEMOTOLOGY 
ID.213 224 6687 
PAGE 
6/20 
APPLICATION FOR 
ACCELERATED REVIEW OF HUMAN GENE TRANSFER EXPERIMENT 
A. BACKGROUND 
Ti tle .: High-Dose Chemotherapy and Autologous Bone Marrow plus Peripheral Blood Stem 
Cell Transplantation for Patients with Lymphoma or Metastatic Breast Cancer: Use of 
Marker Genes to Investigate the Biology of Hematopoietic Reconstitution in Adults. 
Principal Investigator: Dan Douer, MD 
Co-Investigators: Alexandra M. Levine, MD, W. French Anderson, MD, Maria Gordon, 
MD, Susan Groshen, PhD, Aziz Khan, MD, Ann M. Mohrbacher, MD, Franco Muggia, MD, 
Darryl Shibata, MD. 
Participating Institutions: USC/Norris Cancer Center, LAC/USC Medical Center 
B. VECTOR, TARGET CELL, AND TRANSDUCTION PROCEDURES 
1 . The proposed gene is the neomycin resistant gene (Neo R ). 
The protocol will use 2 vectors: G1 Na and LNL6. 
2. Both vectors have previously been approved by the RAC and used in dinical 
protocols. 
Both G1 Na and LNL6 were approved for the Protocol titled - 
'Genetic Marking with retroviral vectors to study the feasibility of stem cell gene 
transfer and the biology of hematopoietic reconstitution after autologous 
transplantation in multiple myeloma, chronic myelogenous leukemia or metastatic 
breast cancer". Principal Investigator: Cynthia E. Dunbar. M.D.. Clinical 
Hematology Branch. NHLBI. published In Human Gene Therapy 9:205-222. 1993. 
3. The vector supplier Is Genetic Therapy Inc, Gaithersburg, MD. In the future, 
dinical grade LNL6 will also be supplied by the Vector Producing Unit (VPU) at the 
Norris Cancer Center of the University of Southern California, Los Angeles, CA. 
A separate IND application will be submitted when the VPU becomes operational. 
4. The target cells for transduction are CD34+ enriched bone marrow and peripheral 
blood progenitor cells (PBPC). 
5. The median (range) rate of transduction of the proposed vectors in individually 
picked CFU-GM colonies in our laboratory is: 
Bone marrow cells - 7% (0-33%). (n= 4) 
PBPC 37% (0-60%) (n= 4) 
6. The median (range) level of gene expression in the target cells is: 
Bone marrow cells - 2.2% (0-26%) (n= 4) 
PBPC -5.5% <1 -1 1 .7%) (n= 4) 
Recombinant DNA Research, Volume 20 
[533] 
