Federal Register / VoL 5B,. No. 31/ Thursday,. Febcuary lfi,. lflaa / Notice* 
9 * 03 - 
at which, it will be reviewed; written 
comments from the primary reviewers 
>4 weeks before the RAC meeting; and 
written responses from the Principal 
Investigators £2 weeks before the 
meeting. 
“Oral Presentations at RAC Meetings 
provide only a brief overview of the 
proposal; they should concentrate on 
questions raised by the reviewers before 
and at the meeting;. Oral presentations 
should be <20 minutes: £10- minutes for 
the overview and <110 minutes for 
responses to the reviewers’ questions. 
“II. Reviewers' Responses: 
“Written Reviews should emphasize 
issues related to gene marking, gene 
transfer or gene therapy. They should 
state explicitly whether the Points to 
Consider have been addressed 
satisfactorily, and should examine the 
scientific rationale, scientific context 
(relative to other proposals reviewed by 
the RAC), whether the preliminary in 
vitro and in vivo data were obtained in 
appropriate models and are sufficient, 
and whether questions related to safety, 
efficacy, and social and ethical context 
have been resolved. Whenever possible, 
criticisms of Consent Forms should 
include suggested revisions for the RAC 
to consider — provided as written 
alternatives. Review's should also state 
whether the proposal is: 
“(a) Acceptable as written, 
“(b) Acceptable with specific 
revisions or after satisfactory responses 
to specific questions raised on review, 
or 
“(c) Unacceptable in its present form. 
“Oral Discussion of Reviews at the 
RAC Meeting. It should be possible to 
present most reviews orally within £5 
minutes.” 
B. Addition of Appendix D-XXXTV to 
the N1H Guidelines 
The following section is added to 
Appendix D: 
“Appendix D-XXXTV. 
“Dr. Michael T. Lotze, University of 
Pittsburgh, Pittsburgh, Pennsylvania, 
can conduct experiments on twenty 
patients with metastatic, and/or 
unresectable, locally advanced 
melanoma, renal cell carcinoma, breast 
cancer, or colon cancer who have failed 
standard therapy. Patients will receive 
multiple subcutaneous injections or 
autologous tumor cells combined with 
an autologous fibroblast cell line that 
has been transduced in vitro with the 
gene coding for Interleukin-4 (IL-4) to 
augment the in vivo antitumor effect. 
Patients will be monitored for antitumor 
effect by PCR analysis and multiple 
biopsy of the injection site.” 
C. Addition of Appendix D-XXXV to the 
NIH Guidelines 
The following section is added to 
Appendix D: 
"Appendix D— XXXV. 
“Dr. Friedrich G. Schuening, Fred 
Hutchinson Cancer Research Center, 
Seattle, Washington, can conduct 
human gene’ transfer experiments on 
patients £18' years of age with breast 
cancer, Hodgkin’s disease, or non- 
Hodgkin’s lymphoma. A total of 10 
patients per year will be enrolled in the 
studies over a period of four years. 
Patients will undergo autologous bone 
marrow transplantation with a selected 
population of Interleukin-3 (IL-3) or 
granulocyte colony-stimulating factor 
(G-CSF) stimulated CD34(+)jperipheral 
blood repopulating cells (PBRC) that 
have been transduced with the gene 
coding for neomycin resistance (neo K ) 
using the retroviral vector, LN. Patients 
will be continuously monitored for neo R 
to determine the relative contribution of 
autologous PBRCs to long-term 
hematopoietic reconstitution. 
Demonstration of long-term contribution 
of autologous PBRC to hematopoiesis 
will enable the use of PBRC alone for 
autologous transplants and suggest the 
use of PBRC as long-term carriers of 
therapeutically relevant genes.” 
D. Addition of Appendix D-XXXV1 to 
the NIH Guidelines 
The following section is added to 
Appendix D: . 
“Appendix D-XXXVI. 
“Dr. Friedrich G. Schuening, Fred 
Hutchinson Cancer Research Center, 
Seattle, Washington, can conduct 
human gene transfer experiments on 
patients £ 18 years of age with breast 
cancer, Hodgkin’s disease, or non- 
Hodgkin’s lymphoma. A total of 5 
patients per year will be enrolled in the 
study over a period of four years. 
Patients will undergo allogeneic bone 
marrow transplant with granulocyte 
colony-stimulating factor (G-CSF) 
stimulated CD34(+) PBRC harvested 
from an identical twin that have been 
transduced with neo R using the 
retroviral vector, LN. Patients will be 
continuously monitored for neo R to 
determine the relative contribution of 
G— CSF stimulated allogeneic PBRCs to 
long-term bone marrow engraftment. 
Demonstration of long-term contribution 
of allogeneic PBRC to hematopoiesis 
will enable the use of PBRC alone for 
allogeneic transplants and suggest the 
use of PBRC as long-term carriers of 
therapeutically relevant genes.” 
E. Addition- of Appendix D-XXXVU to 
the NIH Guidelines 
The following section is added to 
Appendix D: 
•'Appendix D-XXXVII. 
“Dr. Malcolm K. Brenner of St. Jude 
Children’s Hospital, Memphis, 
Tennessee, and Dr. Bonnie J. Mills of 
Baxter Healthcare Corporation, Santa 
Ana, California, can conduct a 
multicenter uncontrolled human gene 
transfer experiment on 12 patiant&£21 
years of age with Stage D Neuroblastoma 
in first or second marrow remission. 
Autologous bone marrow cells will be 
separated into two fractions, purged and 
unpurged. Each fraction will be 
transduced with the neo R gene by either 
LNL6 or GlNa. Patients will be 
monitored by the polymerase chain 
reaction (PCR) for the presence of neo R . 
The protocol is designed to evaluate the 
safety and efficacy of the Neuroblastoma 
Bone Marrow Purging System following 
high dose chemotherapy.” 
F. Addition of Appendix D-XXXV1II to 
the NIH Guidelines 
The following section is added to 
Appendix D: 
“Appendix D-XXXVHI. 
“Drs. Carolyn Keierleber and Ann 
Progulske-Fox of the University of 
Florida, Gainesville, Florida, can 
conduct experiments involving the 
introduction of a gene coding for 
tetracycline resistance into 
Porphyromonas gingivalis at a physical 
containment level of Biosafety Level-2 
(BL— 2).” 
G. Addition of Appendix D-XXXIX to 
the NIH Guidelines 
The following section is added to 
Appendix D: 
‘'Appendix D-XXXIX. 
“Dr. Scott M. Freeman of Tulane 
University Medical Center, New 
Orleans, Louisiana, can conduct 
experiments on patients with epithelial 
ovarian carcinoma who have clinical 
evidence of recurrent, progressive, or 
residual disease who have no other 
therapy available to prolong survival. 
Patients will be injected 
intraperitoneally with the irradiated 
PA-1 ovarian carcinoma cell line which 
has been transduced with the herpes 
simplex thymidine kinase (HSV-TK) 
gene. The patients will then receive 
ganciclovir therapy. Previous, data 
indicates that HSV-TK+ tumor cells 
exhibit a killing effect on HSV-TK - 
cells when exposed to ganciclovir 
therapy. Patients will be evaluated for 
safety and side effects of this 
treatment.” 
OMB’s “Mandatory Information 
Requirements for Federal Assistance 
[54] 
Recombinant DNA Research, Volume 17 
