Federal Register / Vol. 59, No. 29 / Friday, February 11, 1994 / Notices 
6703 
Exogenously Administered Human 
Alpah-1 Antitrypsin Gene in the 
Respiratory Tract of Humans. 
V. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Transfer Protocol/Dr. Freedman 
On January 5. 1994, Dr. Ralph 
Freedman of the MD Anderson Gancer 
Center, Houston, Texas, resubmitted a 
human gene transfer protocol to the 
Recombinant DNA Advisory Committee 
for formal review and approval. The 
title of this protocol is: Use of a 
Retroviral Vector to Study the 
Trafficking Patterns of Purified Ovarian 
Tumor infiltrating Lymphocytes fTIL) 
Used in Intraperitonea! Adoptive 
Immvmotherapy of Ovarina Cancer 
Patients — ^A Pilot Study. 
Dr. Freedman first submitted this 
protocol on March 22, 1993. During the 
June 7-8, 1993, RAC meeting, this 
protocol was deferred until the 
investigators could return to the full 
RAC with the following information: (l) 
Data demonstrating efficient 
transduction ofYlL, (2) sufficient 
information regarding demonstration of 
selectivity, i.e., specific trafficking of 
TIL to tumor, (3) complete statistical 
analysis, (4) revised Informed Consent 
document in simplified language, and 
(5) address concerns about patient 
responsibility for research-related costs. 
The motion to defer the protocol 
pending full RAC review of additional 
information passed by a vote of 18 favor, 
0 opposed, and no abstentions. 
VI. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Transfer Protocol/Dr. Vogelzang 
On January 6, 1994, Dr. Nicholas 
Vogelzang, University of Chicago, 
Chicago, Illinois, submitted a human 
gene transfer protocol to the 
Recombinant DNA Advisory Committee 
for formal review and approval. The 
title of this protocol is: Phase I Study of 
Immunotherapy for Metastatic Renal 
Cell Carcinoma by Direct Gene Transfer 
into Metastatic Lesions. 
Vn. Addition to Appendix D of the NIH 
Guidelines Regarding a Human Gene 
Transfer Protocol/Dr. Roth 
On January 4, 1994, Dr. Jack A. Roth 
of the MD Anderson Cancer Center, 
University of Texas, Houston, Texas, 
resubmitted a human gene transfer 
protocol to the Recombinant DNA 
Advisory Committee for formal review 
and approval. The title of this protocol 
is: CJinical Protocol of Modification of 
Oncogene and Tumor Suppressor Gene 
Expression in Non-Small Cell Luiig 
Cancer (NSCLC). 
Dr. Roth first submitted this protocol 
on March 19. 1992. During the 
September 14-15, 1992, RAC meeting, 
approval of this protocol was 
recommended contingent on the review 
and approval of the following 
information by RAC primary reviewers 
(Drs. Miller. Hirano, and Geiduschek): 
(1) Data demonstrating the transforming 
potential of 100 milliliters of retroviral 
supernatant analogous to the 
preparation that will be used for the 
clinical protocol, (2) data obtained from 
in vitro mixing experiments, (3) in vitro 
data demonstrating that the new vector 
preparations have activity, and (4) 
incorporation of minor changes in the 
Informed Consent document as noted by 
Drs. Carmen and Hirano. The motion 
passed by a vote of 18 in favor, 0 
opposed, and no abstentions. On May 
11, 1993, Dr, Roth submitted material in 
response to the RAC’s stipulations for 
approval and a request for the following 
modifications: (1) The producer cell line 
will be amended to include 
GP+ehvAMl2, and (2) the clinical 
protocol grade supernatant will be 
produced by Microbiological Associates. 
On June 15. 1993, the primary reviewers 
agreed to the modification of 
stipulation, #1, as requested by Dr. Roth. 
The revised stipulation is: (1) submit 
data demonstrating the transforming 
potential of a single patient dose, i.e., 
10ml of retrovirus supernatant at 1 x 
10* CFTI/ml. The primary reviewers did 
not accept subsequent data submitted by 
Dr. Roth as adequately fulfilling tlie 
stipulations for approval of the protocol. 
For this reason, the primary reviewers 
requested that the materials submitted 
by Dr. Roth should be reviewed by the 
full RAC at its December 2-3, 1993, 
meeting. During the December ! 993 
meeting, the consensus of the RAC was 
that the protocol was considered 
administratively inactivated; therefore, 
RAC approval of the protocol was 
withdrawn. The RAC recommended that 
Dr, Roth submit a revised protocol 
including all additional data for review 
by the full RAC. based on the following: 
(1) Failure of the primary reviewers to 
recommend approval of the protocol. (2) 
lengthy delays in the presentation of 
data. (3) the fact that there are several 
new members who were not on the RAC 
at the time the original protocol was 
reviewed, and (4) the proposed use of a 
new vector. The RAC noted that if Dr. 
Roth submits a revised protocol for full 
RAC review, new primary reviewers 
will be assigned. The RAC 
recommended that the Office of 
Recombinant DNA Activities forward a 
letter to Dr. Roth with recommendations 
for resubmission of his protocol for full 
RAC review. The Office of Recombinant 
DNA Activities forw'arded a letter to Dr. 
Roth on December 21, 1993, requesting 
submission of a revised protocol by 
February 4, 1994. 
VII. Addition to Appendix D of the NIH 
Guidelines Regarding Deliberate 
Transfer of a Chloramphenicol 
Resistance Gene to an Avirulent Strain 
of Rickettsia prowzaeki/Dr. Policastro 
On January 4, 1994, Dr. Paul 
PoUcastro of the National Institutes of 
Health, Rocky Mountain Laboratories, 
Hamilton, Montana, resubmitted a 
request regarding the deliberate transfer 
of a gene coding for chloramphenicol 
resistance to ^ avirulent strain of 
Rickettsia prowzaeki. 
Dr. Policastro first submitted this 
request on March 23, 1993. During its 
June 7-8, 1993, meeting, the RAC 
deferred approval of this request by a 
vote of 20 in favor, 0 oppos^, and no 
abstentions. *1110 RAC deferred approval 
until the investigator submits the 
following data for full RAC review: (1) 
Data demonstrating that the construct is 
safe and- useful, and (2) in vitro data 
demonstrating the selective advantage of 
chloramphenicol resistance over other 
selectable markers. 
DC. Report on Minor Modifications to 
NIH-Approved Human Gene Transfer 
Protocols 
Dr. LeRoy Walters, RAC Chair, will 
present an update on minor 
modifications to NIH-approved human 
gene transfer protocols. 
X. Amendments to Footnotes 21 and 22 
and Section III-A-3 of the NIH 
Guidelines Regarding Recombinant 
DNA Vaccines 
Dr. Leonard Post, Chair of the 
Working Group on Vaccines, will 
present an overview of the proposed 
amendments to Footnotes 21 and 22. 
The proposed amendments will define 
those categories of experiments 
involving the administration of 
recombinant DNA vaccines that are 
exempt from RAC review and National 
Institutes of Health and Institutional 
Biosafety Committee approval. 
Recombinant DNA Research, Volume 19 
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