Recombinant DNA Advisory G)mmittce - 6/9-10/94 
was protecting the public from hazards associated with the recombinant DNA aspects. 
Dr. Straus recommended that the RAC should proceed cautiously in their deliberation of 
this new technology, i.e., direct DNA injection into muscle. Though probably a safe 
strategy, the proposal would be more acceptable with evidence that an immune response 
can be developed to murine CEA in a murine model. Dr. Smith noted that safety issues 
may vary depending on the life expectancy of the subject. Dr. Post commented that the 
treatments that the subjects have already received is far more toxic than the risks posed 
by the integration of a few DNA molecules. 
Dr. Parkman reminded the committee that whatever action it takes on this protocol will 
have set a precedent. It is important that the RAC remain consistent so that future 
investigators have a clear understanding of the requirements and the committee 
maintains credibility. Dr. Walters asked Dr. Parkman to estimate the time that would be 
required to perform the relevant preclinical murine experiments. Dr. Parkman 
responded that 6-9 months would be an approximate speculation. 
Dr. Lobuglio stated that he was not aware that the CEA gene had been cloned from a 
murine library. Each mouse strain has different immune responses; therefore, several 
different strains would have to be evaluated before drawing any conclusions. He noted 
that the murine model may not be totally predictive of the human experiment. A 
substantial amount of information exists on the use of this technology to produce 
immune responses that are efficacious against infectious diseases. Other investigators 
have demonstrated the antitumor potential of this model by mixing the splenocytes of 
immunized animals with tumor cells, and injecting them into naive animals. Total 
protection against tumor growth was observed in vitro at a ratio of 1:1, an amazingly high 
response. 
Dr. Haselkorn said that he favors approval of this protocol. He asked the investigators 
to submit the immunological data derived from this study to the RAC as soon as 
possible. He said that it is unacceptable that data is unavailable from the vaccinia-CEA 
study after 20 patients have been entered onto the study. 
Dr. Straus said that in absence of preclinical data involving the murine CEA gene or 
relevant data from animal tumor model, clinical data from the vaccinia-CEA trial would 
be an acceptable alternative. Dr. Straus said that he cannot recommend approval of this 
protocol without reviewing these supporting data. 
Dr. Saha asked whether the fact that different mouse strains respond differently to CEA 
is due to major histocompatibility complex (MHC) restriction. Dr. Lx)buglio answered 
that lack of a consistent immune response is one reason that animal models will not be 
totally relevant to the human study. 
Dr. Parkman agreed with Dr. Straus that the clinical data from the vaccinia-CEA study 
would be acceptable data to support this protocol. Dr. Haselkorn objected to inclusion 
of this contingency for approval since these data are from other laboratories and beyond 
Recombinant DNA Research, Volume 19 
[321] 
