Federal Register / Vol. 58. No. 175 / Monday. September 13, 1993 / Notices 
47907 
patients' lung will be transduced with 
‘ the El deleted, replication-incompetent 
adenovirus vector, Ad.CB-CFTR using a 
bronchoscope for gene delivery. Ad.CB- 
! CFTR contains the human gene 
. encoding the cystic fibrosis 
transmembrane conductance regulator 
(CFTR) protein. Pulmonary biopsies will 
be obtained by bronchosopy at 4 days, 
6 weeks, and 3 months following 
treatment. Patients will be monitored for 
evidence of CFTR gene transfer and 
expression, immunological responses to 
j| CFTR or adenovirus proteins, and 
toxicity." 
OMB's "Mandatory Information 
Requirements for Federal Assistance 
j Program Announcements" (45 FR 
39592) requires a statement concerning 
i the official government programs 
contained in the Catalog of Federal 
[ Domestic Assistance. Normally NIH lists 
in its announcements the number and 
title of affected individual programs for 
the guidance of the public. Because the 
j guidance in this notice covers not only 
virtually every NIH program but also 
essentially every Federal research 
program in which DNA recombinant 
molecule techniques could be used, it 
has been determined to be not cost 
effective or in the public interest to 
attempt to list these programs. Such a 
list would likely require several 
additional pages. In addition, NIH could 
not be certain that every Federal 
program would be included as many 
Federal agencies, as well as private 
organizations, both national and 
international, have elected to follow the 
NIH Guidelines. In lieu of the 
individual program listing, NIH invites 
readers to direct questions to the 
information address above about 
whether individual programs listed in 
the Catalog of Federal Domestic 
Assistance are affected. 
Dated: August 25, 1993. 
Ruth L. Kirschstein, 
Acting Director, National Institutes of Health. 
(FR Doc. 93-22260 Filed 9-10-93; 8:45 ami 
BILLING CODE 414O-01-M 
Recombinant DNA Research: Actions 
Under the Guidelines 
AGENCY: National Institutes of Health, 
PHS, DHHS. 
ACTION: Notice of actions under the NIH 
Guidelines for Research Involving 
Recombinant DNA Molecules. 
SUMMARY: This notice sets forth twelve 
actions to be taken by the Director. 
National Institutes of Health (NIH), 
under the May 7, 1986, NIH Guidelines 
for Research Involving Recombinant 
DNA Molecules (51 FR 16958). 
FOR FURTHER INFORMATION CONTACT: 
Additional information can be obtained 
from Dr. Nelson A. Wivel, Director, 
Office of Recombinant DNA Activities 
(ORDA), Office of Science Policy and 
Technology Transfer, National Institutes 
of Health. Building 31, room 4B11, 
Bethesda, Maryland 20892, (301) 496- 
9838). 
SUPPLEMENTARY INFORMATION: Today 
twelve actions are being promulgated 
under the NIH Guidelines for Research 
Involving Recombinant DNA Molecules. 
These twelve proposed actions were 
published for comment in the Federal 
Register of August 19, 1992 (57 FR 
37680), and May 4. 1993 (58 FR 26676), 
and reviewed and recommended for 
approval by the NIH Recombinant DNA 
Advisory Committee (RAC) at its 
meetings on September 14—15, 1992 and 
June 7-8, 1993. 
I. Background Information and 
Decisions on Actions Under the NIH 
Guidelines. 
A. Addition of Appendix D-XLVII to the 
NIH Guidelines 
In a letter dated December 16, 1992, 
Dr. Hilliard F. Seigler of the Duke 
University Medical Center, Durham, 
North Carolina, indicated the 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: A Phase I Trial of Human Gamma 
Interferon-Transduced Autologous 
Tumor Cells in Patients with 
Disseminated Malignant Melanoma. 
This request was published for 
comment in the Federal Register of 
February 12. 1993 (58 FR 8500). 
The protocol was reviewed and 
recommended for deferral during the 
RAC meeting of March 1-2, 1993, by a 
vote of 16 in favor, 1 opposed, and 1 
abstention. Approval of the protocol 
was deferred until the investigators 
submit the following data for full RAC 
review: (l) Generation of cytotoxic T 
lymphocytes (CTL) for human 
peripheral blood lymphocyte from 
tumor-bearing patients in response to 
transduced autologous tumor, (2) 
quantitative correlation between Class I 
antigen expression and the amount of 
human gamma-interferon (IFN), and (3) 
quantitative correlation between the 
number of CTLs generated per unit of 
human gamma-IFN. 
In a letter dated April 9. 1993, Dr. 
Seigler resubmitted the human gene 
therapy protocol with additional data to 
the Recombinant DNA Advisory 
Committee for formal review and 
approval. 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 20 in favor, 0 opposed, and no 
abstentions. The following section may 
be added to Appendix D: 
"Appendix D-XLVII 
"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 retrovirus vector, 
pHuy-IFN, that contains the gene 
encoding human y-IFN. 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." 
I accept this recommendation, and 
Appendix D-XLVII of the NIH 
Guidelines will be added accordingly. 
B. Addition of Appendix D-XLVIII to 
the NIH Guidelines 
In a letter dated April 10, 1993, 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, 
submitted 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 
cDNA for Human Glucocerebrosidase 
into Hematopoietic Stem Cells of 
Patients with Gaucher Disease. 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. The following section may 
be added to Appendix D: 
"Appendix D-XLVUI 
"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 
Recombinant DNA Research, Volume 18 
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