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hetteral Register / Vol. 55, No. 177 / Wednesday. September 12, 1990 / Notices 
e. The full data from the Milan experiments 
and any related data be provided for review 
by a subcommittee of this committee prior to 
a meeting of the Recombinant DNA Advisory 
Committee and that a formal review of those 
data be brought to the Recombinant DNA 
Advisory Committee when this protocol 
comes up for approval. 
7. That a Gnal version of the inclusion/ 
exclusion criteria reflect the parameters that 
were addressed in the subcommittee 
discussion, including the age and length of 
time on PEG-ADA: and 
B. That a specific protocol be provided for 
the follow-up evaluation of the 
immunological and clinical status. 
This request was published for 
comment in the Federal Register of June 
27. 1990 (55 FR 26348). 
During the meeting on July 30, 1990, 
the Human Gene Therapy Subcommittee 
discussed the eight points that were 
enumerated at the meeting of June 1. 
1990. The responses to these points and 
the modifications in the protocol were 
deemed to be satisfactory. Accordingly, 
the subcommittee recommended to the 
Recombinant DNA Advisory Committee 
approval of the protocol in its current 
form. 
During the meeting on July 31. 1990, 
the Recombinant DNA Advisory 
Committee met to review the protocol 
and recommendations from the 
subcommittee. FoUowii^ lengthy 
discussion, the Recombinant DNA 
Advisory Committee by a vote of 16 in 
favor. 1 opposed, and no abstentions, 
approved the protocol with the following 
section to be added to appendix D: 
Appendix E>-XV 
Drs. R. Michael Blaese and W. French 
Anderson of the National Institutes of Health, 
Bethesda, Maryland, can conduct 
experiments in v^hich a gene coding for 
adenosine deaminase (.ADA) will be inserted 
into T lymphocytes of patients with severe 
combined immunodeficiency disease, using a 
retroviral vector, LNL8. Following the 
insertion of the gene, the T lymphocytes will 
be reinfused into the patients. The patients 
will then be followed for evidence of clinical 
improvement in their disease state, and 
measurement of multiple parameters of 
immune function by laboratory testing. 
Approval is based on the following two 
stipulations: 
1. That intraperitonea! administration of 
transduced T lymphocytes not be used before 
clearance by the Chairs of the Human Gene 
Therapy Subcommittee and the Recombinant 
DNA Advisory Committee; and 
2. That the number of research patients be 
limited to 10 at this time. 
I accept this recommendation, and 
Appendix D-XV of the NIH Guidelines 
will be added accordingly. 
C. Addition of Appendix D-XVI of the 
NIH Guidelines 
In a letter dated June 13, 1990, Dr. 
Steven A. Rosenberg of the National 
Institutes of Health indicated his 
intention to submit a human gene 
therapy protocol to the Human Gene 
Therapy Subcommittee and the 
Recombinant DNA Advisory Committee. 
The title of this protocol is “Gene 
■flierapy of Patients with Advanced 
Cancer using Tumor Infiltrating 
Lymphocytes Transduced with the Gene 
Coding for Tumor Necrosis Factor." 
This request was published for 
comment in the Federal Register on June 
27, 1990 (55 FR 26348). 
The Human Gene Therapy 
Subcommittee considered the request at 
its meeting on July 30, 1990. After 
extensive discussion, the subcommittee 
decided that the three provisions listed 
below, as requested by the Nlli 
Institutional Biosafety Committee, had 
been adequately addressed by the 
investigator. They are: 
1. Performance of primate toxicity studies; 
2. Studies using neutralizing antibody to 
tumor necrosis factor, and 
3. Additional data from experiments. which 
study the trafficking patterns of tumor 
infiltrating lymphocytes. 
The subcommittee then recommended 
to the Recombinant DNA Advisory 
Committee approval of the protocol. 
The protocol was presented to the 
Recombinant DNA Advisory Committee 
at its meeting of July 31. 1990. 
During the deliberation, the 
Recombinant DNA Advisory Conunittee 
considered matters related to the 
toxicity of tumor necrosis factor (TNF) 
in patients, and the means by which 
such toxicity would be treated. 
Finally, the protocol was approved by 
a vote of 17 in favor, 0 opposed, and no 
abstentions, with the provision that the 
final consent form be reviewed 
administratively by the NIH Office for 
Protection frmn Research Risks and that 
the NIH Institutional Biosafety 
Committee approve the final revised 
version of the protocol. 
As a result, the following section will 
be added to Appendix D: 
Appendix D-XVI 
Dr. Steven A. Rosenberg of the National 
Institutes of Health, Bethesda, Mary'lacd, can 
conduct experiments on patients with 
advanced melanoma who have failed all 
effective therapy. These patients will be 
treated with escalating doses of autohjgous 
tumor infiltrating lymphocytes (TIL) 
transduced with a gene coding for tumor 
necrosis factor. Escalating numbers of 
transduced TTL will be administered at three 
weekly intervals along with the 
administration of inlerleukin-2. The objective 
is to evaluate the toxicity and possible 
therapeutic efficacy of the administration of 
tumor infiltrating lymphocytes (TIL) 
transduced with the gene coding for tumor 
necrosis factor (TNF). 
I accept this recommendation, and 
appendix D-XVI of the M// Guidelines 
will be added accordingly. 
D. Amendment to the "Points to 
Consider in the Design and Submission 
of Protocols for the Transfer of 
Recombinant DNA into the Genome of 
Human Subjects” 
During the meeting of June 1, 1990, the 
Human Gene Therapy Subcommittee 
recommended a pnx^ure for 
expediting reviews on approved human 
gene therapy protocols. The following 
policy was proposed for discussion, 
approval, and addition to the document 
entitled, "Points to Consider in the 
Design and Submission of Protocols for 
the Transfer of Recombinant DNA into 
the Genome of Human Subjects." The 
proposal is as follows: 
A minor change in a protocol approved by 
the Human Gene Therapy Subcommittee, that 
is, a change that does not significantly alter 
the basic design of a protocol and that does 
not increase risk to the subjects, may be 
approved by die Chair of the Subcommittee if 
the change has also been approved by the 
relevant IRB and by the Institutional 
Biosafety Committee. The Chair will report 
on any such approvals at the next regularly 
scheduled meeting of the Subcommittee. 
This amendment was published for 
conunent in the Federal Register on June 
27, 1990 (55 FR 26348). 
The Recombinant DNA Advisory 
Committee considered this amendment 
at its meeting on July 31, 1990. The intent 
of this amendment is to allow minor 
changes in protocols without having to 
wait for the next scheduled meetings of 
the RAC Human Gene Therapy 
Subcommittee and the Recombinant 
DNA Advisory Committee. No such 
provision existed in the original Points 
to Consider document. 
After discussion, the Recombinant 
DNA Advisory Committee approved the 
amendment with a vote of 17 in favor, 0 
opposed, and no abstentions. The 
following section will be added to the 
"Points to Consider" document: 
V. Minor Modifications 
A minor cliange in protocol approved by 
the Hmnan Gene Therapy Subcommittee and 
the Recombinant DNA Advisory Committee 
is a change that does not significantly alter 
the basic design of a protocol and that does 
not increase to the subjects. If the rhanj?*- 
has been approved by the relevant 
Institutifmal^evtew Board. Institutional 
Bioeefety Conunittee, and Chair of the 
Human Therapy Subcommittee, then the 
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Recombinant DNA Research, Volume 14 
