Recombinant DNA Advisory Committee - 3/S-4/94 
virulence. 
Dr. Straus said that the investigator has stated that at low multiplicity of infection^ this 
organism (Strain E) causes only mild disease in humans, a condition used for vaccine 
studies. But in the proposed experiments, the laboratory personnel are expected to be 
exposed to higher doses of the organism that could cause serious symptoms. Dr. Carmen 
asked about possible Biosafety Level 4 facilities. Dr. Wivel stated that there are four 
such facilities in the United States. 
Committee Motion 
A motion was made by Dr. Post and seconded by Dr. DeLeon to defer the proposal. 
The proposal was deferred by a vote of 13 in favor, 0 opposed, and no abstentions. The 
proposal was deferred based on the following: (1) chloramphenicol is one of the two 
antibiotics of choice for the treatment of Rickettsia infection; (2) strain E (proposed for 
this study) is considered to be of reduced virulence not avirulent; Strain E has been 
reported to revert to the virulent state after passages ex vivo\ and (3) data is unavailable 
demonstrating the probability of reversion to a virulent strain when grown under large- 
scale conditions, i.e., between 1 x 10’ and 1 x 10^® organisms. 
The RAC discussed possible scenarios under which this proposal might be eligible for 
resubmission for RAC review: (1) if the gene encoding for virulence were identified, or 
(2) the investigator submits a request for use of this organism in a Biosafety Level 4 
facility contingent on the destruction of residual stocks upon optimization of 
transformations assays. The RAC emphasized that resubmission of the proposal will not 
guarantee RAC approval. 
XII. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: PHASE I STUDY OF 
IMMUNOTHERAPY FOR METASTATIC RENAL CELL CARCINOMA BY DIRECT 
GENE TRANSFER INTO METASTATIC LESIONS/DR, VOGELZANG 
Review— Dr. Doi 
Dr. Walters called on Dr. Doi to present his primary review of the protocol submitted by 
Dr. Nicholas J. Vogelzang of the University of Chicago, Chicago, Illinois. Dr. Doi 
explained that the proposed study is very similar to Dr. Gary J. Nabel's (Protocol #9306- 
045) and Dr. Joseph Rubin's (Protocol #9312-064) previously approved by the RAC. 
This study will be conducted on 15 HLA-B7 negative patients with metastatic renal cell 
carcinoma. Patients will receive direct intratumoral injections of a cationic liposome 
complex containing the plasmid vector, pHLA-B7/P-2 microglobulin. This vector 
expresses a heterodimeric cell surface protein consisting of HLA-B7 and (i-2 
microglobulin. Expression of this protein should induce an in vivo antitumor immune 
response. The objectives of this study are to determine a safe and effective dose of the 
vector, confirm in vivo expression, and characterize the immune response. The only 
difference between this proposal and those of Drs. Nabel and Rubin is the tumor type 
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Recombinant DNA Research, Volume 19 
