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Federal Register / Vol. 58, No. 175 / Monday, September 13, 1993 / Notices 
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." 
I accept this recommendation, and 
Appendix D-XLV1II of the N!H 
Guidelines will be added accordingly. 
C. Addition of Appendix Lf-XLEX to the 
NIH Guidelines 
In a letter dated April 9, 1993, Dr. 
Gary J. Nabel of the University of 
Michigan Medical Center, Ann Arbor. 
Michigan, submitted a human gene 
therapy protocol to the Recombinant 
DNA Advisory Committee for formal 
review and approval. The title of this 
protocol is: A Molecular Genetic 
intervention for AIDS — Effects of a 
Transdominant Negative Form of Rev. 
This request was published for 
comment in the Federal Register of May 
4. 1993 (58 FR 26676). 
The protocol was reviewed and 
recommended for approval during the 
RAC meeting of June 7—8, 1993, by a 
vote of 14 in favor, 0 opposed, and 4 
abstentions. Approval of the protocol 
was contingent on the submission of a 
revised Informed Consent document 
including the following: (l) A 
recommendation that contraception be 
used by males as well as females, and 
(2) a request for autopsy in the event of 
death, and (3) an explanation of long- 
term patient follow-up. 
On June 15, 1993, Dr. Nabel submitted 
the modified Informed Consent 
document. The modified Informed 
Consent document was reviewed by a 
primary reviewer of the protocol, and it 
was determined that it meets the request 
of the RAC. The following section may 
be added to Appendix D: 
"Appendix D-XLIX 
“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 M10, a transdominant inhibitory 
mutant of the rev gene of the human 
immunodeficiency virus (HIV). 
Transduction of the rev mutant will be 
mediated either by the retrovirus vector, 
PLJ-cREV M10, or a plasmid DNA/ 
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 HTV infection 
to CD4( + ) cells." 
I accept this recommendation, and 
Appendix D-XLIX of the NIH 
Guidelines will be added accordingly. 
D. Addition of Appendix D-L to the NIH 
Guidelines 
In a letter dated April 9, 1993, Dr. 
Gary J. Nabel of the University of 
Michigan Medical Center, Ann Arbor, 
Michigan, submitted a human gene 
therapy protocol to the Recombinant 
DNA Advisory Committee for formal 
review and approval. The title of this 
protocol is: Immunotherapy for Cancer 
by Direct Gene Transfer into Tumors. 
This request was published for 
comment in the Federal Register of May 
4. 1993 (58 FR 26576). 
The protocol was reviewed and 
recommended for approval during the 
RAC meeting of June 7-8, 1993, by a 
vote of 19 in favor, 0 opposed, and 1 
abstention. 
No restrictions were placed on the 
types of tumors to be treated. Approval 
of the protocol was contingent on the 
review and approval of materials 
submitted in response to the following 
stipulations: (1) A revised patient 
eligibility section including the 
provision that patients who are eligible 
for catheter delivery of cationic 
liposomes must have a performance 
status of 0-1, and (2) a revised Informed 
Consent document including a 
recommendation that male/ female 
patients use contraception and females 
not be pregnant or plan to become 
pregnant while participating in the 
study, an explanation of long-term 
follow-up, and a request for autopsy in 
the event of death. 
On June 15, 1993, Dr. Nabel submitted 
the modified patient eligibility section 
and a modified Informed Consent 
document. These documents were 
reviewed by the primary reviewers of 
the protocol, and it was determined that 
it meets the request of the RAC. The 
following section may be added to 
Appendix D: 
“Appendix D-L 
“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 histocompatibility 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 fdr 
enhanced immune responses against 
tumor cells, and safe and effective doses 
will be determined." 
I accept this recommendation, and 
Appendix D-L of the NIH Guidelines 
will be added accordingly. 
E. Addition of Appendix D-LJ to the 
NIH Guidelines 
In a letter dated March 26, 1993, Dr. 
John A. Barranger of the University of 
Pittsburgh, Pittsburgh, Pennsylvania, 
indicated his intention to submit 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 Gaucher Disease: Ex Vivo Gene 
Transfer and Autologous 
Transplantation of CD34(+) Cells. This 
request was published for comment in 
the Federal Register of May 4, 1993 (58 
FR 26676). 
The protocol was reviewed and 
recommended for approval during the 
RAC meeting of June 7-8, 1993, by a 
vote of 15 in favor, 0 opposed, and 4 
abstentions. Approval of the protocol 
was contingent on review and approval 
of materials submitted in response to 
the following stipulations: (1) A 
maximum of 5 patients will be entered 
into the study, (2) patients will not 
receive cyclophosphamide ablation of 
bone marrow, (3) patients who 
demonstrate antibodies against 
glucocerebrosidase (GC) will not be 
eligible for this protocol, (4) GC enzyme 
replacement therapy will not be 
discontinued until cytochemical 
evidence of engraftment is 
demonstrated, and (5) the Informed 
Consent document will be revised to 
include a recommendation that male/ 
female patients use contraception and 
females not be pregnant or plan to 
become pregnant while participating in 
the study, an explanation of long-term 
follow-up, a request for autopsy in the 
event of death, patient protection from 
media inquiries, and a statement 
informing the patients that although 
they may receive no direct benefit from 
the protocol, knowledge may be gained 
that will benefit others. 
On June 11, 1993, Dr. Barranger 
submitted a modified protocol and 
Informed Consent document. These 
documents were reviewed by the 
primary reviewers of the protocol, and 
it was determined that it meets the 
request of the RAC The following 
section may be added to Appendix D: 
“Appendix D-LI 
“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 
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Recombinant DNA Research, Volume 18 
