Recombinant DNA Advisory Committee - 12/1-2/94 
The RAC approved a motion made by Dr. Haselkorn and seconded by Dr. Brinckerhoff to accept the protocol 
submitted by Dr. dayman by a vote of 16 in favor, 1 opposed, and 1 abstention. Approval of the protocol is 
contingent on the review and approval of the following by the primary RAC reviewers: (1) Development of a 
sensitive screening assay (preferably biologic — e.g., the HPV assay), to detect the presence of p53 mutants in 
the adenovirus vector stocks. In the event that a mutant is identified, that stock will be discarded. (2) The 
specific p53 mutation will be characterized for all subjects undergoing gene transfer. (3) Submission of a 
detailed description of the analyses that will be conducted on available post-mortem tissue. 
Ms. Meyers expressed her concern about approving this protocol before vector safety has been demonstrated 
in this biological system. 
Dr. Walters noted that a vote for approval of the protocol requires that the investigator satisfactorily meet all 
stipulation requirements prior to forwarding the proposal to the NIH Director for approval. 
Summary 
Dr. Gary L. dayman of The University of Texas - M.D. Anderson Cancer Center, Houston, Texas, may 
conduct gene transfer experiments on 21 subjects (> 18 years of age). Subjects will receive intratumoral 
injections of the replication-defective type 5 adenovirus vector, Ad5CMV-p53, which contains the normal 
human p53 tumor suppressor gene. The El region of Ad5CMV-p53 has been replaced with a p53 expression 
cassette containing the human CMV promoter. Subjects will be divided into 2 cohorts: (1) those with 
surgically accessible tumors, and (2) those with non-resectable tumors. This dose-escalation study involves 
multiple administrations of Ad5CMV-p53. The objectives of the study are to: (1) determine the maximum 
tolerated dose of Ad5CMV-p53, (2) determine qualitative and quantitative toxicity, and (3) document 
antitumor activity. 
XL CHAIR REMARKS/DR. WALTERS 
On behalf of the entire committee, Dr. Walters presented 4 outgoing RAC members with certificates of 
appreciation for their dedicated service to the RAC. He thanked the outgoing members for their tireless 
contributions to the rapidly developing field of human gene therapy. The outgoing members are: (1) 
Alexander Capron, LL.B., Professor, University of Southern California, Los Angeles, California; (2) Roy Doi, 
Ph.D., Professor, University of California, Davis, California; (3) Constance Brinckerhoff, Ph.D., Professor, 
Dartmouth Medical School, Hanover, New Hampshire; and (4) Robert Haselkorn, Ph.D., Professor, University 
of Chicago, Chicago, Illinois. 
XII. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN GENE TRANSFER 
PROTOCOL ENTITLED; GENE THERAPY OF PRIMARY AND METASTATIC MALIGNANT TUMORS 
OF THE LIVER USING ACN S3 VIA HEPATIC ARTERY INFUSION: A PHASE I STUDY/DRS. VENOOK 
AND WARREN 
Review-Dr. Erickson 
Dr. Walters called on Dr. Erickson to present his primary review of the protocol submitted by Drs. Alan 
Venook and Robert Warren of the University of California, San Francisco, California. Dr. Erickson explained 
that this protocol involves adenovirus vector delivery of the human p53 gene to subjects with hepatic metastasis 
from colorectal cancer or hepatocellular carcinoma. Patient eligibility will be limited to subjects who have p53 
defects. p53 is a tumor suppressor gene. Correction of the defective gene may decrease tumor growth. The 
rationale for this proposal is similar to the rationale for Dr. dayman’s protocol; therefore, many of the 
concerns are similar. The protocol is presented very well. Some of the concerns regarding the extent of virus 
infection will be ascertained either by laparoscopic exploration or needle biopsy rather than evaluation of post- 
mortem tissue. 
[464] 
Recombinant DNA Research, Volume 20 
