Federal Register / Vol. 58, No. 175 / Monday, September 13, 1993 / Notices 
47909 
: 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 
j blood leukocytes. Patients currently 
| receiving GC replacement therapy and 
I 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responsiveness will be withdrawn from 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.” 
I accept this recommendation, and 
Appendix D-LJ of the NIH Guidelines 
will be added accordingly. 
F. Addition of Appendix D-LII to the 
I NIH Guidelines 
In a letter dated July 20, 1992, Drs. 
Robert Walker and R. Michael Blaese, 
I National Institutes of Health, Bethesda, 
Maryland, submitted a human gene 
transfer protocol to the Recombinant 
I DNA Advisory Committee for formal 
review and approval. The title of this 
protocol is: A Study of the Safety and 
Survival of the Adoptive Transfer of 
Genetically Marked Syngeneic 
Lymphocytes in Human 
j Immunodeficiency Virus (HIV) Infected 
| Identical Twins. This request was 
published for comment in the Federal 
Register of August 19, 1992 (57 FR 
37680). 
The protocol was reviewed and 
recommended for approval during the 
RAC meeting of September 14-15, 1992, 
by a vote of 19 in favor, 0 opposed, and 
no abstentions. Approval of the protocol 
was contingent on the following 
stipulations: (1) The investigators may 
use the vector supernatants currently in 
storage: however, any future vector 
preparations will be tested by long-term 
culturing of the packaging line 
following vector supernatant harvest, (2) 
the Informed Consent document should 
be divided into two separate documents, 
one for gene marking and the other for 
the therapeutic aspects, and (3) the 
section of the donor Informed Consent 
document describing the 
lymphopheresis procedure should be 
moved before the section describing the 
required travel schedule. 
On July 15, 1993, Dr. Walker 
submitted a modified Informed Consent 
document. This document was 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-LII 
“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 anti-CD3 
and interleukin-2. The enriched 
population of cells will be transduced 
with either LNL6 or GlNa, which 
contain the neo* gene. The transduced 
cells will be expanded in tissue culture 
and administered to the HIV-infected 
twin. Patients wall be monitored for 
immune function and the presence of 
marked cells.” 
I accept this recommendation, and 
Appendix D-LII of the NIH Guidelines 
will be added accordingly. 
G. Addition of Appendix D-LII to the 
NIH Guidelines 
In a letter dated April 5, 1993, Dr. 
Corey Raffel of the Childrens Hospital 
Los Angeles, Los Angeles, California, 
and Dr. Kenneth Culver of Iowa 
Methodist Medical Center, Des Moines, 
Iowa, 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 the Treatment of 
Recurrent Pediatric Malignant 
Astrocytomas with In Vivo Tumor 
Transduction with the Herpes Simplex 
Thymidine Kinase Gene. 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 19 in favor, 0 opposed, and no 
abstentions. Approval of the protocol 
was contingent on the following 
stipulation: (1) The investigators must 
submit a document that will inform 
children of the experimental procedures 
and associated risks. 
On July 13, 1993, Dr. Raffel submitted 
the document. This document was 
reviewed by two RAC members. 
Additional changes were requested, and 
the investigator incorporated those 
changes. It was determined that the 
revised document met the request of the 
RAC. The following section may be 
added to Appendix D: 
"Appendix D-LHI 
"Dr. Cory Raffel of the Childrens 
Hospital Los Angeles, 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.” 
I accept this recommendation, and 
Appendix D-LIII of the NIH Guidelines 
will be added accordingly. 
H. Addition of Appendix D-LTV to the 
NIH Guidelines 
On April 9, 1993, a human gene 
therapy protocol was submitted for 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, by Dr. Bruce 
Merchant, Viagene, Inc., San Diego, 
California (sponsor of the protocol), to 
the Recombinant DNA Advisory 
Committee for formal review and 
approval. The title of this protocol is: A 
Preliminary Study to Evaluate the Safety 
and Biologic Effects of Murine 
Retroviral Vector Encoding HIV-1 
Genes [HrV-IT(V)] in Asymptomatic 
Subjects Infected with HIV-1. 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 16 in favor, 0 opposed, and 2 
abstentions. Approval of the protocol 
was contingent on the following 
stipulations: (l) The Informed Consent 
document must include a request for 
autopsy, and (2) the formulation of the 
excipient that will be used for the 
retrovirus vector preparation must be 
submitted for review. 
On June 11, 1993, Dr. Donald 
Longenecker of Viagene, Inc., submitted 
the formulation of the vector 
preparation; and on June 23, 1993, Dr. 
Rose Hermanson of Viagene, Inc., 
submitted the revised Informed Consent 
document. These documents were 
reviewed by two RAC members, and it 
was determined that it meets the request 
of the RAC. The following section may 
be added to Appendix D: 
"Appendix D-LIV 
“Dr. Jeffrey E. Galpin of the 
University of Southern California, Los 
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