Recombinant DNA Advisory Committee - 3/3-4/94 
I 
investigators will not obtain informed consent from their own patients, and (3) 
statements will be included in the Informed Consent document regarding long-term 
patient follow-up and a request for autopsy. Dr. Parkman explained that due to the 
experimental nature of gene transfer at present, these requirements are appropriate. 
Responding to Ms. Meyers' concern about alternative prolastin therapy. Dr. Brigham 
explained that the majority of patients that enter the study will be receive enzyme 
replacement therapy. Prolastin will be discontinued only for a period of 1 month during 
the gene transfer experiment. A 1 month interruption in prolastin therapy will not 
significantly affect the course of the patients' disease. Dr. Brigham agreed to amend the 
statement in the Informed Consent document regarding provision of medical care in the 
event of research-related injury. 
Dr. Brigham expressed his opinion regarding the adequacy of the preclinical studies and 
their pertinence to the human study. He emphasized that extensive expression of the 
transgene was demonstrated using the same vector proposed for the human study. This 
AAT protocol differs from the cystic fibrosis studies in several important aspects, i.e., 
AAT is a secreted protein that functions in small airways and peripheral alveoli of the 
lungs; therefore, the animal experiments were designed to demonstrate transgene 
expression in these areas rather than in trachea and large bronchi as was demonstrated 
for the cystic fibrosis protocols. The liposome delivery method is not novel and has been 
approved by the RAC for several other protocols. 
Committee Motion 
A motion was made by Dr. Parkman and seconded by Dr. Secundy to approve the 
protocol contingent on the review and approval of the following by the primary 
reviewers: (1) transduction efficiency data demonstrating a rate of 10-15% transduction 
in situ, and (2) a revised Informed Consent document that includes statements describing 
the possibility of systemic absorption of vector DNA, the necessity for long term follow- 
up, and a request for autopsy. The motion for approval passed by a vote of 12 in favor, 
0 opposed, and 1 abstention. 
Dr. Post abstained from voting due to a conflict of interest (collaborates with Dr. Leaf 
Huang, a co-investigator on this study). 
VIII. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED; USE OF A RETROVIRAL VECTOR TO 
STUDY THE TRAFFICKING PATTERNS OF PURIFIED OVARIAN TUMOR 
INFILTRATING LYMPHOCYTES (TIL) USED IN INTRAPERITONEA L ADOPTIVE 
IMMUNOTHERAPY OF OVARIAN CANCER PATIENTS - A PILOT STUDY /DR, 
FREEDMAN 
Review-Dr. Brinckerhoff (presented by Dr. Dronamraju) 
Dr. Walters called on Dr. Dronamraju to summarize Dr. Brinckerhoffs written primary 
review of the protocol submitted by Dr. Ralph Freedman of MD Anderson Cancer 
Recombinant DNA Research, Volume 
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