Federal Register / Vol. 58, No. 199 / Monday, October 18, 1993 / Notices 
53815 
containing the cystic fibrosis 
transmembrane conductance regulator 
(CFTR) cDNA, Ad.CB-CFTR. A single 
dose of 10*. 3x109 or 10* • pfu/ml will be 
administered to the nasal cavity of 3 
patients in each dose group. Patients 
will be monitored by nasal lavage and 
biopsy to assess safety and restoration of 
normal epithelial function.” 
I accept this recommendation, and 
Appendix D-LVU of the NIH Guidelines 
will be added accordingly. 
C. Addition of Appendix D-LVU1 to the 
NIH Guidelines 
In a letter dated September 9, 1992, 
Dr. Joyce A. O’Shaugnnessy of the 
National Institutes of Health, Bethesda, 
Maryland, indicated her attention to 
submit a human gene therapy protocol 
to the Recombinant DNA Advisory 
Committee for formal review and 
approval. The title of this protocol is: 
Retroviral Mediated Transfer of the 
Human Multi-Drug Resistance Gene 
(MDR-1) into Hematopoietic Stem Cells 
During Autologous Transplantation after 
Intensive Chemotherapy for Breast 
Cancer. 
During the December 3-4, 1992, 
Recombinant DNA Advisory Committee 
meeting, the protocol was deferred until 
the investigators submitted the 
following for full RAC review: (1) Data 
demonstrating that human CD34(+) cells 
can be transduced in vitro with the 
actual vector that will be used for the 
human clinical protocol, (2) a 
description of the methods that will be 
used to monitor gene expression in bone 
marrow and tumor cells, and (3) a 
description of the endpoint for 
determining bone marrow recovery, i.e., 
comparison of gene amplification and 
the rate of polymorphonuclear 
leukocyte recovery following taxol 
administration. 
On July 14, 1993, Dr. O'Shaughnessy 
resubmitted a human gene therapy 
protocol for RAC review and approval. 
This request was published for 
comment in the Federal Register of 
August 18, 1993 (58 FR 44098). 
The protocol was reviewed and 
recommended for approval during the 
RAC meeting of September 9-10, 1993 
by a vote of 17 in favor, 0 opposed, and 
no abstentions. The following section 
may be added to Appendix D. 
“Appendix D-LVIII. 
“Dr. Joyce A. O’Shaughnessy of the 
National Institutes of Health, Bethesda, 
Maryland, may conduct experiments on 
18 patients (18-60 years old) with Stage 
IV breast cancer who have achieved a 
partial or complete response to 
induction chemotherapy. This study 
will determine the feasibility of 
obtaining engraftment of CD34(+) 
hematopoietic stem cells transduced by 
a retroviral vector, GlMD, and 
expressing a cDNA for human multi- 
drug resistance-1 (MDR-1) gene 
following high dose chemotherapy, and 
whether the transduced MDR-1 gene 
confers drug resistance to hematopoietic 
cells and functions as an in vivo 
dominant selectable marker. Patients 
will be monitored for evidence of 
myeloprotection and presence of the 
transduced MDR-1 gene." 
I accept this recommendation, and 
Appendix D-LVIII of the NIH 
Guidelines will be added accordingly. 
D. Addition of Appendix D-LIX to the 
NIH Guidelines 
On July 12, 1993, Drs. Larry E. Kun, 
R.A. Sanford, Malcolm Brenner, and 
Richard L. Heideman of SL Jude 
Children’s Research Hospital. Memphis, 
Tennessee, and Dr. Edward H. Oldfield 
of the National Institutes of Health, 
Bethesda, Maryland, submitted a human 
gene therapy protocol to the 
Recombinant DNA Advisory Committee 
for formal review and approval. The 
title of this protocol is: Gene Therapy 
for Recurrent Pediatric Brain Tumors. 
This request was published for 
comment in the Federal Register of 
August 18, 1993 (58 FR 44098). 
The protocol was reviewed and 
recommended for approval during the 
RAC meeting of September 9-10, 1993 
by a vote of 17 in favor, 0 opposed, and 
no abstentions. The RAC requested that 
the Office of Recombinant DNA 
Activities send a letter to the 
Institutional Review Board strongly 
recommending that the Informed 
Consent document should be separated 
into two separate documents: (1) A 
patient assent form, and (2) a guardian 
consent form. On September 21, 1993, 
the Office of Recombinant DNA 
Activities sent a letter to the 
Institutional Review Board at the St. 
Jude Children’s Research Hospital and 
the LeBonheur Children’s Medical 
Center regarding the Committee’s 
recommendations. The following 
section may be added to Appendix D: 
“Appendix D-LIX. 
“Drs. Larry E. Kun, R.A. Sanford, 
Malcolm Brenner, and Richard L. 
Heideman of St. Jude Children’s 
Research Hospital, Memphis, 
Tennessee, and Dr. Edward H. Oldfield 
of the National Institutes of Health, 
Bethesda, Maryland, may conduct 
experiments on 6 patients (3-21 years 
old) with progressive or recurrent 
malignant supratentorial tumors 
resistant to standard therapies. Mouse 
cells producing the retroviral vector 
containing the herpes simplex 
thymidine kinase gene (GlTKSVNa) 
will be instilled into the tumor areas via 
multiple stereotactically placed 
cannulas. Patients will be treated with 
ganciclovir to eliminate cells expressing 
the transduced gene. Patients will be 
monitored for central nervous system, 
hematologic, renal or other toxidties, 
and for anti-tumor responses by 
magnetic resonance imaging studies. 
1 accept this recommendation, and 
Appendix D-LIX of the NIH Guidelines 
will be added accordingly. 
E. Addition of Appendix D-LX to the 
NIH Guidelines Regarding Semliki 
Forest Virus 
Dr. Gary F. Temple of Life 
Technologies, Inc., Gaithersburg, 
Maryland, submitted a request for a 
reduction in physical containment from 
Biosafety Level 3 to Biosafety Level 2 for 
a Semliki Forest Virus (SFV) vector 
expression system. 
During the September 14-15, 1992, 
Recombinant DNA Advisory Committee 
meeting, the request was deferred so 
that the investigators could acquire data 
regarding the following: (1) The 
frequency of recombination that 
produces replication-competent virus, 
using cell numbers analogous to the 
laboratory setting (e.g., 1x10* cells), and 
(2) acquire data regarding the frequency 
of seropositivity among personnel 
previously exposed to SFV. 
During the June 7-8, 1993, 
Recombinant DNA Advisory Committee 
meeting, the request was deferred until 
the investigators returned to the 
Committee with the following: (1) A 
product information sheet informing 
customers of the potential health risks 
associated with the expression system, 
standard methods to be used for virus 
inactivation, a helper virus assay to 
detect SFV, and a description of 
symptoms and procedures to be 
followed in the event that SFV infection 
occurs in a laboratory worker (including 
methods to prevent transfer to insect 
vectors and environmental spread); and 
(2) SFV inactivation data. 
In a letter dated February 8, 1993, Dr. 
Temple resubmitted a request for a 
reduction in physical containment from 
Biosafety Level 3 to Biosafety Level 2 for 
a SFV vector expression system. This 
request was published for comment in 
the Federal Register on August 18, 1993 
(58 FR 44098). 
During the September 9-10, 1993, 
Recombinant DNA Advisory Committee 
meeting, this request was reviewed and 
recommended for approval by a vote of 
13 in favor, 2 opposed, and 1 abstention. 
The physical containment for Life 
Technologies, Inc., SFV vector 
expression system may be reduced from 
Biosafety Level 3 to Biosafety Level 2. 
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