Recombinant DMA Advisory Committee - 3/3-4/94 
committee under both the Ministry of Research and Ministry of Agriculture that oversees 
viral biosafety and scientific issues of human gene therapy. Six proposals have been 
reviewed including studies of gene marking and gene transfer in diseases such as 
adenosine deaminase deficiency, cystic fibrosis, glioblastoma, and melanoma. In France, 
once a proposal is approved by this dual committee, the clinical trial can be initiated 
without further review by other agencies. 
Dr. Walters remarked that recently a report has been published entitled: Experimental 
(Somatic) Gene Therapy, Ethical Concerns and Controls from Dr. M.A.M. de Wachter, 
Instituut voor Gezondheidsethiek, Maastrict, The Netherlands. This report surveyed 
human gene transfer studies and their oversight mechanisms in Europe. Once 
permission has been obtained from the publisher, copies will be made available to RAC 
members. 
XV. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED; CLINICAL PROTOCOL FOR 
MODIFICATION OF ONCOGENE AND TUMOR SUPPRESSOR GENE EXPRESSION 
IN NON-SMALL CELL LUNG CANCER/mL ROTH 
Review— Dr. Motulsky 
Dr. Walters called on Dr. Motulsky to present his primary review of the protocol 
submitted by Dr. Jack A. Roth of the Anderson Cancer Center, Houston, Texas. 
This protocol is a resubmission of a protocol that was contingently approved by the RAC 
at its September 1992 meeting. At its December 1993 meeting, the consensus of the 
RAC was that Dr. Roth should resubmit 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 that occurred, (3) there are 
several new members on the RAC who were not on the committee at the time the 
original protocol was reviewed, and (4) Dr. Roth requested the use of a substitute vector. 
The RAC agreed that new primary reviewers would be assigned for the resubmitted 
protocol. Tlie RAC informed Dr. Roth that this study was considered administratively 
inactivated; therefore, RAC approval of the protocol was withdrawn. 
Dr. Motulsky explained that recent scientific advances have led to an understanding of 
oncogenes (i.e., Yi-ras and their role in tumor cell proliferation) and tumor suppressor 
genes (i.e., p53 and their role in suppressing tumor growth). Although normal p53 is a 
tumor suppressor gene, introduction of certain mutations can confer oncogenic capacity 
to p53. The investigator proposes to use the retroviral construct, AS-K-ras, to express 
antisense RNA in an attempt to block the function of the K-ras oncogene. Another 
construct, LNp55B, will be employed to express wild-type p53 in an attempt to suppress 
tumor growth. Most of the preclinical animal experiments were performed with the 
retroviral construct LNSX-p55, which is different from the vector currently proposed for 
the human study. Additional studies have been submitted in a human lung tumor/nude 
mouse model demonstrating marked suppression in tumor growth in response to 
intrabronchial injection of the LNp53 construct. The RAC must consider the likelihood 
[501 
Recombinant DNA Research, Volume 19 
