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Federal Register / Vol. 58, No. 31 / Thursday, February 18, 1993 / Notices 
in first or second marrow remission. 
Autologous bone marrow cells will be 
separated into two fractions, purged and 
j unpurged. Each fraction will be 
transduced with the neo R gene by either 
i LNL6 or GlNa. Patients will be 
monitored by the polymerase chain 
j reaction (PCR) for the presence of neo H . 
The protocol is designed to evaluate the 
safety and efficacy of the Neuroblastoma 
Bone Marrow Purging System following 
| high dose chemotherapy.” 
1 accept this recommendation and 
jl| Appendix D-XXXVII of the NIH 
Guidelines will be added accordingly. 
i F. Addition of Appendix D-XXXV11I to 
the N1H Guidelines 
In a letter dated July 1, 1992, Drs. 
j Carolyn Keierleber and Ann Progulske- 
Fox of the University of Florida, 
l! Gainesville, Florida, requested 
j permission to conduct experiments 
which involve the introduction of a 
jl gene coding for tetracycline resistance 
i into Porphyromonas gingivalis at 
Biosafety Level 2. 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 on September 14-15, 
1992, by a vote of 15 in favor, 0 
opposed, and 1 abstention. The 
following section may be added to 
Appendix D: 
“Appendix D-XXXVIII. 
“Drs. Carolyn Keierleber and Ann 
Progulske-Fox of the University of 
Florida, Gainesville, Florida, can 
conduct experiments involving the 
i introduction of a gene coding for 
tetracycline resistance into 
Porphyromonas gingivalis at a physical 
containment level of Biosafety Level-2 
(BL-2)." 
I accept this recommendation and 
Appendix D-XXXVIII of the NIH 
Guidelines will be added accordingly. 
G. Addition of Appendix D-XXXIX to 
the NIH Guidelines 
In a letter dated Mav 10, 1990, Dr. 
Scott M. Freeman of the University of 
j Rochester School of Medicine, 
Rochester, New York, indicated his 
intention to submit a human gene 
therapy protocol to the Human Gene 
Therapy Subcommittee (HGTS) and the 
RAC for formal review and approval. 
The title of this protocol is: "Gene 
, Transfer for the Treatment of Cancer.” 
This request was published for 
comment in the Federal Register on July 
I 2, 1991 (56 FR 30398). 
The protocol was reviewed during the 
I HGTS meeting on July 29-30, 1991. 
Provisional approval was given with the 
stipulation that the PA-1 ovarian cancer 
cell line be tested for potential 
pathogens as per FDA guidelines. 
Further, it was requested that more 
preclinical studies on the MFG vector 
should be performed in order to assure 
the absence of replication-competent 
retroviruses. Dr. Freeman submitted the 
requested documentation to ORDA. The 
HGTS forwarded the protocol to the 
RAC for consideration during the 
October 7-8, 1991, meeting. This 
request was published for comment in 
the Federal Register on September 3, 
1991 (56 FR 43686). 
The protocol was reviewed during the 
RAC meeting on October 7-8, 1991. The 
RAC passed a motion to defer approval 
of the protocol by a vote of 19 in favor, 
0 opposed, and no abstentions. The RAC 
stated that the protocol may be 
considered again when the following 
criteria have been met: 
(i) Improve the animal model so that 
it has some relevance to the malignancy 
that is observed in patients; 
(ii) Examine the animal model for the 
tumor specificity of cytotoxic T 
lymphocytes; 
(iii) Demonstrate the efficacy of this 
proposed treatment by measuring the 
tumor burden in patients and state 
whether this will be done by 
laparoscopy, imaging, or both; 
(iv) Refine safety tests; and 
(v) Eliminate every reference to the 
term cancer vaccine in the patient 
consent form. 
In a telephone conversation with Dr. 
Wivel on January 2, 1992, and a follow- 
up letter dated January 7, 1992, Dr. Scott 
M. Freeman indicated his intention to 
resubmit his revised protocol to the 
RAC for formal review and approval. 
The request was published for comment 
in the Federal Register on January 3, 
1992 (57 FR 316). 
During the meeting on February 10, 
1992, the RAC met to review the 
protocol. There was discussion 
regarding the safety data, and the use of 
the term vaccine. The investigator 
agreed to delete all reference to the term 
vaccine since the protocol is designed to 
evaluate the effect of TK+ on TK- cells, 
not an immune response. After lengthy 
discussion, the RAC, by a vote of 10 in 
favor, 4 opposed and no abstentions, 
approved the protocol pending receipt 
of additional safety data that 
demonstrates transduced, irradiated 
cells are not producing replication- 
competent helper viruses or generating 
rescued TK+ virus. 
On December 10, 1992, Dr. Freeman 
submitted to ORDA the additional safety 
data relative to the cell line, PA-l-STK. 
The data was reviewed by the RAC 
primary reviewer, and it was 
determined that it meets the request of 
the RAC. The following section mav h« 
added to Appendix D: 
“Appendix D-XXXIX. 
“Dr. Scott M. Freeman ofTulane 
University Medical Center, New 
Orleans, Louisiana, can conduct 
experiments on patients with epithelial 
ovarian carcinoma who have clinical 
evidence of recurrent, progressive, or 
residual disease who have no other 
therapy available to prolong survival. 
Patients will be injected 
intraperitoneally with the irradiated 
PA-1 ovarian carcinoma cell line which 
has been transduced with the herpes 
simplex thymidine kinase (HSV-TK) 
gene. The patients will then receive 
ganciclovir therapy. Previous data 
indicates that HSV-TK+ tumor cells 
exhibit a killing effect on HSV-TK- 
cells when exposed to ganciclovir 
therapy. Patients will be evaluated for 
safety and side effects of this 
treatment." 
I accept this recommendation and 
Appendix D-XXXIX of the NIH 
Guidelines will be added accordingly. 
II. Summary of Actions 
A. Addition to the Points to Consider in 
the Design and Submission of Protocols 
for the Transfer of Recombinant DNA 
into the Genome of Human Subjects 
Regarding Submission Requirements for 
Human Gene Transfer/Gene Therapy 
Protocols 
The following section is added to the 
Points to Consider: 
“Guidelines for the Submission and 
Review of Human Gene Transfer/ 
Tharapy Protocols for Review by the 
Recombinant DNA Advisory Committee 
“I. Investigator-Submitted Material: 
"Written proposals should begin with 
the lay and scientific abstracts, followed 
by the Points to Consider and the 
material provided in the body of an R01 
(sections A-D). When a proposal has 
been submitted previously, there should 
be a short section (£200 words) 
immediately following the abstracts that 
summarizes major revisions since the 
last review. Length limitations are 4-5 
pages for the Points to Consider, 2 pages 
each for CVs (Biosketch format) and 20 
pages for the body of the proposal 
(excluding tables, figures, appendices, 
and manuscripts). Data provided must 
include a description of the elements in 
the vector, the source of that 
information, and the method by which 
sequence data were compiled, plus 3 
diskettes with the vector sequence in 
ASCR format. Written material from 
Principal Investigators must be 
submitted £8 weeks before the meeting 
Recombinant DNA R esearch, Volume 17 
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