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Federal Register / Vol. 57. No. 78 / Wednesday. April 22, 1992 / Notices 
Guidelines. The request was published 
for comment in the Federal Register on 
January 3. 1992 (57 FR 316). 
During the meeting on February 11. 
1992. the RAC met to review this 
request Hie basis of this request resides 
in the fact that CDC/NIH biosafety 
guidelines, that were published in 1964. 
recommended biosafety level 2 practices 
for M. avium. M. avium is ubiquitous in 
nature, a common contaminant in the 
soil, and there is no evidence that direct 
transmission occurs between humans. 
The RAC, by a vote of 14 in favor. 0 
opposed, and no abstentions, approved 
the lowering of the classification of 
Mycobacterium avium from a Class III 
bacterial agent to a Class II bacterial 
agent M. avium would move from 
Appendix B-I-C-l to Appendix B-I-B-l 
in the NIH Guidelines. 
I accept this recommendation and 
Appendices B-I-C-l and B-I-B-l of the 
NIH Guidelines will be amended 
accordingly. 
II. Summary of Actions 
A. Addition of Appendix D-XX1V to the 
NIH Guidelines 
The following section is added to 
appendix D: 
Appendix D-XXTV 
Dr. Gary J. Mabel of the University of 
Michigan Medical School Ann Arbor, 
Michigan, can conduct gene therapy 
experiments on twelve patients with 
melanoma or adenocarcinoma. Patient 
population will be limited to adults over the 
age of IB and female patients most be 
postmenopausal or have undergone tubal 
ligation or orchiectomy. The patient's immune 
response will be stimulated by the 
introduction of a gene encoding fora Class I 
MHC protein, HLA-B7, In order to enhance 
tumor regression. DNAfliposqme-medicatd 
transfection techniques will be used to 
directly transfer this foreign gene into tumor 
cells. HLA-B7 expression will be confirmed 
in vivo, and the immune response stimulated 
by the expression of this antigen will be 
characterized. These experiments will be 
analyzed for their efficacy in treating cancer. 
B. Addition of Appendix D-XXV to the 
NIH Guidelines 
The following section is added to 
appendix D: 
Appendix D-XXV 
Dr. Kenneth Cometta of Indiana 
University, Indianapolis, Indiana, can 
conduct gene transfer experiments on up to 
10 patients with acute myetogeoous leukemia 
(AML) and up to 10 patients with acute 
lymphocytic leukemia (ALL). The patient 
population will be limited to persons between 
18 and 85 years of age. Using the LNL-6 
vector, autologous bone marrow cells will be 
marked with the neomycin resistance gene. 
Gene marked and untreated bone marrow 
cells will be reinfused at the time of bone 
marrow transplantation. Patients will then be 
monitored for evidence of the neomycin 
resistance gene in peripheral blood and bone 
marrow cells in order to determine whether 
relapse of their disease Is a result of residual 
malignant cells remaining in the harvested 
marrow or inadequate ablation of the tumor 
cells by chemotherapeutic agents. 
Determining the source of relapse may 
indicate whether or not purging of the bone 
marrow is a necessary procedure for these 
leukemia patients. Further studies will be 
performed in order to determine the 
percentage of leukemic cells that contain the 
LNL-6 vector and the donality of marked 
cells. 
C. Addition of Appendix D-XXVI to the 
NIH Guidelines 
The following section is added to 
appendix D: 
Appendix D-XXVI 
Dr. James S. Economou of the University of 
California. Los Angeles, can conduct gene 
transfer experiments on 20 patients and with 
metastatic melanoma and 20 patients with 
renal cell carcinoma. These patients will be 
treated with various combinations of tumor- 
infiltrating lymphocytes and peripheral blood 
leukocytes, including CD8 and CD4 subsets of 
both types of cells. These effector cell 
populations will be given in combination with 
interleukin-2 (IL-2) to the melanoma patients 
and IL-2 plus alpha interferon in the renal 
cell carcinoma patients. The effector cells 
will be transduced with the neomycin 
resistance gene using either the LNIB or GlN 
retroviral vectors. This “genetic marking" of 
the tumor-infiltrating lymphocytes and 
peripheral blood lymphocytes is designed to 
answer questions about the trafficking of 
these cells, their localization to tumors, and 
their in vivo lifespan. 
D. Addition of Appendix D-XXVI1 to die 
NIH Guidelines 
The following section is added to 
appendix D; 
Appendix D-XXYH 
Dr. Philip D. Greenberg of the University of 
Washington. Seattle, Washington, can 
conduct gene transfer experiments on up to 
15 HIV seropositive patients undergoing 
allogeneic bone marrow transplantation for 
non-Hodgkin*s lymphoma evaluate toe 
safety and efficacy of HTV -specific cytotoxic 
T lymphocyte (CTL) therapy. CTL wdl be 
transduced with a retroviral vector (HyTK) 
encoding a gene that h a fusion product of 
the hygromydn phosphotransferase gene 
(HPH) and the 'rapes virus thymidine kinase 
(HSV-TK) gene. The vector will deliver both 
■ marker gene and a suicide gene in these T 
cell clones in toe event that patients develop 
side effects as a consequence of CTL therapy. 
Data will be correlated over time, looking at 
multiple parameters of HIV disease activity. 
The objectives of these studies tadnde 
evaluating the safety and toxicity of CTL 
therapy, determining the duration of in vivo 
survival of HIV-specific CTL clones, and 
determining if ganciclovir therapy can 
eradicate genetically modified, adoptively 
transferred CTL oells. 
E. Amendment to Appendix D-XV of the 
NIH Guidelines 
Appendix D-XV will read as follows: 
Appendix D-XV 
In addition to the conditions outlined in the 
initial approval patients may be given s 
supplement of a CD-34 + -enriched peripheral 
blood lymphoctyes (PEL) which have been 
placed in culture conditions that favor 
progenitor cell growth. This enriched 
population of cells will be transduced with 
the retroviral vector, ClNaSvAd. GINaSvAd 
is similiar to LASN. et distinguishable by 
PCR. LASN has been used to transduce 
peripheral blood T lymphocytes with the 
ADA gene. Lymphocytes and myeloid cells 
will be isolated from patients over time and 
assayed for the presence of the LASN or 
GINaSvAd vectors. The primary objectives 
of this protocol are to transduce CD 34 + 
peripheral blood cells with the adenosine 
deaminase gene, administer these cells to 
patients, and determine if such cells can 
differentiate into lymphoid and myeloid cells 
in vivo. There is a potential for benefit to the 
patients in that these hematopoietic 
progenitor cells may survive longer, and 
divide to yield a broader range of gene- 
corrected cells. 
F. Amendment to Introduction, Section 
II and V of the Points to Consider 
Regarding Review by the Human Gene 
Therapy Subcommittee; Amendment to 
Sections II1-A and IV -C of the NIH 
Guidelines. 
The following sections will be 
amended in the NIH Guidelines: 
Sections IH-A, IV-C-l-b-(lJ. section 
IV-C-2, section IV-C-3-b-(lJ, section 
IV--C-3-b-{2)). The amended sections 
will read: 
Section IH-A. Experiments That Require 
RAC Review and NIH and IBC Approval 
Before Initiation. 
Experiments to this category cannot be 
initiated without submission of relevant 
information on the proposed experiment to 
NIH. the publication of the proposal in the 
Federal Register for 15 days of comment, 
review by toe RAC and specific approval by 
NIH. The containment conditions for such 
experiments will be recommended by the 
RAC and set by NIH a! the time of approval. 
Such experiments also require * * *. 
Section IV-C-l-b-{l). Major Actions. To 
execute major actions, the Director. NDHl 
must seek the advice of the RAC and provide 
an opportunity for public and Pederal agency 
comment Specifically, the agenda of toe RAC 
meeting citing the major actions will be 
published in the Federal Register at least 15 
days before the meeting, and the Director. 
NIH. will also publish the proposed actions in 
the Federal Register for comment at least 15 
days before the meeting. In addition, the 
Director’s proposed decision, at htsftier 
discretion may be published to the Federal 
Register for 15 days of comment before final 
action is taken The Director’s final decision 
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Recombinant DNA Research, Volume 15 
