Federal Register / Vol. 58, No. 175 / Monday, September 13, 1993 / Notices 
47911 
I accept this recommendation, and 
Section III— A— -4 of the NIH Guidelines 
and the Points to Consider will be 
amended accordingly. 
II. Summary of Actions 
A. Addition of Appendix D-XLVII to the 
NIH Guidelines 
The following section is added to 
Appendix D: 
“Dr. Hilliard F. Seigler of Duke 
University Medical Center, Durham, 
North Carolina, may conduct 
experiments on 20 patients with 
disseminated malignant melanoma. 
Autologous tumor cells will be 
transduced with a retroviral vector, 
pHuy-IFN, that contains the gene 
encoding human y-fFN. Following 
lethal irradiation, the transduced cells 
will be readministered to patients for 
the purpose of generating cytotoxin T 
cells that are tumor specific along with 
the up-regulation of Class I major 
histocompatibility antigens. Patients 
will be monitored for clinical regression 
of tumors and generation of tumor- 
specific cytotoxic T lymphocytes.” 
B. Addition of Appendix D-XLVIII to 
the NIH Guidelines 
The following section is added to 
Appendix D: 
“Drs. Stefan Karlsson and Cynthia 
Dunbar of the National Institutes of 
Health, Bethesda, Maryland, and Dr. 
Donald B. Kohn of the Childrens 
Hospital of Los Angeles, Los Angeles, 
California, may conduct experiments on 
10 patients with Gaucher disease. 
CD34(+) hematopoietic stem cells will 
be isolated from bone marrow or from 
peripheral blood treated with 
granulocyte-colony stimulating factor. 
CD34(+) cells will be transduced with a 
retrovirus vector, GlGc, containing 
cDNA encoding human 
glucocerebrosidase and administered 
intravenously. Patients will be 
monitored for toxicity and 
glucocerebrosidase expression.” 
C. Addition of Appendix D-XLIX to the 
NIH Guidelines 
The following section is added to 
Appendix D: 
"Dr. Gary J. Nabel of the University of 
Michigan Medical Center, Ann Arbor, 
Michigan, may conduct experiments on 
12 patients with AIDS to be divided into 
4 experimental groups. CD4(+) 
lymphocytes will be isolated from 
peripheral blood and transduced with 
Rev MlO, a transdominant inhibitory 
mutant of the rev gene of thehuman 
immunodeficiency virus (HTV). 
Transduction of the rev mutant will be 
mediated either by the retrovirus vector. 
PLJ-cREV MlO, or a plasmid DNA 1 
liposome complex. Patients will be 
monitored for survival of the transduced 
CD4(+) cells by polymerase chain 
reaction and whether Rev MlO can 
confer protection against HIV infection 
to CD4(+) cells.” 
D. Addition of Appendix D-L to the NIH 
Guidelines 
The following section is added to 
Appendix D: 
“Dr. Gary J. Nabel of the University of 
Michigan Medical Center, Ann Arbor, 
Michigan, may conduct experiments on 
24 patients with advanced cancer. 
Patients will undergo in vivo 
transduction with DNA/liposome 
complexes containing genes encoding 
the HLA-B7 hisotcompatibility antigen 
and beta-2 microglobulin in a non-viral 
plasmid. These DNA/liposome 
complexes will be administered either 
by intratumoral injection or catheter 
delivery. Patients will be monitored for 
enhanced immune responses against 
tumor cells, and safe and effective doses 
will be determined.” 
E. Addition of Appendix D-LI to the 
NIH Guidelines 
The following section is added to 
Appendix D: 
“Dr. John A. Barranger of the 
University of Pittsburgh, Pittsburgh, 
Pennsylvania, may conduct experiments 
on 5 patients with Gaucher disease. The 
CD34(+) hematopoietic stem cells will 
be isolated from peripheral blood and 
transduced in vitro with the retrovirus 
vector, N2-Sv-GC, encoding the 
glucocerebrosidase (GC) enzyme. 
Following reinfusion of the transduced 
cells, patients will be monitored by PCR 
analysis for GC expression in peripheral 
blood leukocytes. Patients currently 
receiving GC replacement therapy and 
who demonstrate clinical 
responsiveness will be withdrawn from 
exogenous GC therapy. Patients not 
previously treated with exogenous GC, 
will be monitored for clinical reversal of 
lipid storage symptoms.” 
F. Addition of Appendix D-LU to the 
NIH Guidelines 
The following section is added to 
Appendix D: 
“Dr. Robert Walker of the National 
Institutes of Health, Bethesda, 
Maryland, may conduct experiments on 
12 HIV-infected patients who have a 
seronegative identical twin. CD4(+) and 
CD8(+) cells will be isolated from the 
seronegative twin and induced to 
polyclonal proliferation with anit-CD3 
and interleukin-2. The enriched 
population of cells will be transduced 
with either LNL6 or GlNa, which 
contain the neo R gene. The transduced 
cells will be expanded in tissue culture 
and administered to the HIV-infected 
twin. Patients will be monitored for 
immune function and the presence of 
marked cells.” 
G. Addition to Appendix D-LIII to the 
NIH Guidelines 
The following section is added to 
Appendix D: 
“Dr. Corey Raffel of the Childrens 
Hospital Los Angeles, California, and 
Dr. Kenneth Culver of Iowa Methodist 
Medical Center, Des Moines, Iowa, may 
conduct experiments on 30 patients 
between 2 and 18 years of age with 
recurrent malignant astrocytoma. 
Fifteen patients will be accrued into this 
study initially. If at least one patient 
responds to therapy, an additional 14 
patients will be treated. Patients with 
either surgically accessible or non- 
accessible tumors will be treated with 
the vector producing cell line (PA317) 
carrying the retrovirus vector, 
GlTkSvNa. This vector will transduce 
tumor cells in vivo with the Herpes 
simplex thymidine kinase (HS-tk) gene 
that renders the cells sensitive to killing 
by ganciclovir. Surgically accessible 
patients will undergo surgical debulking 
of their tumor followed by repeated 
administration of the HS-tk vector 
producer cells into the tumor bed. 
Children with unresectable tumors will 
undergo stereotaxic injection of vector 
producer cells into tumors.” 
H. Addition of Appendix D-LIV to the 
NIH Guidelines 
The following section is added to 
Appendix D: 
"Dr. Jeffrey E. Galpin of the 
University of Southern California, Los 
Angeles, California, and Dr. Dennis A. 
Casciato of the University of California, 
Los Angeles, California, may conduct 
experiments on 15 HIV(+) asymptomatic 
patients. Patients will receive 3 monthly 
intramuscular injections of the 
retrovirus vector (N2lIIBenv) encoding 
the HTV-1 IIIB envelope protein. 
Patients will be monitored for acute 
toxicity, CD4 levels. HIV-specific CTL 
responses, and viral burdens.” 
I. Addition of Appendix D-LV to the 
NIH Guidelines 
The following section is added to 
Appendix D: 
“Drs. Charles Hesdorffer and Karen 
Antman of Columbia University College 
of Physicians and Surgeons, New York, 
New York, may conduct experiments on 
20 patients with advanced breast, ovary, 
and brain cancer. CD34(+) 
hematopoietic stem cells will be 
isolated from bone marrow, transduced 
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