Recombinant DNA Advisory Committee - 03/1-2/93 
Review--Dr. Carmen 
Dr. Carmen stated that this protocol is innovative and fascinating. The investigators 
should describe the differences between transduced and untransduced irradiated cells, 
and the their ability to elicit an immune response. The investigators need to explain the 
differences between the MFG and MFGS vectors. Dr. Carmen said that this protocol is 
very interesting and recommends that it be approved. 
Other Comments 
Ms. Meyers provided comments about the informed consent document. The document 
should contain an explanation of gene therapy, including a lay description of vectors and 
the gene transfer process. A statement should be included about patient confidentiality, 
and that the NIH and the FDA will have access to the patient's records. A section 
should be included about the time frame for patient follow-up and the procedures 
involved. The informed consent document provides a recommendation to women 
regarding the use of contraception; however, this statement should include men. A 
statement should be added about a request for autopsy. 
Dr. Miller provided a description of the proposed vector. This vector is based on the N2 
vector which has been previously reviewed by the RAC. The vector contains the gag 
region of the Moloney murine leukemia virus (M-MuLV) at the 5' end and the env 
sequences of the parental virus at the 3' end. When used in combination with the 
packaging cell line, there is the potential for homologous recombination and the 
generation of helper virus. One of the problems associated with an N2 based vector is 
the large gag open reading frame. Since the gag protein is antigenic, the effects of this 
protein must be considered. 
Dr. Miller explained that the investigators have proposed a new vector, MFGS, in which 
deletions and mutations have been incorporated to eliminate gag protein synthesis. 
However, the RAC must consider that the animal data that has been submitted was 
generated using the MFG vector, not MFGS. The committee should be certain that the 
new animal data, generated with the new vector, correlates with that of the old vector. 
MFGS differs from MFG in that a cryptic splice has been included upstream from gag’, 
therefore, this vector is not new. MFGS is still an N2 based vector. Past experience has 
demonstrated that is very easy to generate helper virus from N2. 
Dr. Miller noted that the LN series was developed in response to the helper virus 
problems associated with N2. In the LN vectors, the env region was deleted in order to 
eliminate the possibility of homologous recombination. The investigators have not 
detected any helper virus associated with the use of the MFG vector; however, there is 
the potential for helper virus production. The MFGS vector has a mutated gag region; 
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Recombinant DNA Research, Volume 17 
