Recombinant DNA Advisory Committee - 12/2-3/93 
Committee Motion #1 
A motion was made by Ms. Grossman and seconded by Ms. Meyers to defer approval of 
the protocol on the basis of inadequate preclinical data. 
Dr. Miller agreed with the investigators' assessment, that published studies adequately 
address the preclinical issues. Additional animal experiments will not add any new 
scientific information. Dr. Parkman said that his principal concern is that the end point 
of this study is to explicitly demonstrate melanoma-specific CTL responses; the data 
inadequately assesses the investigators' competence in performing these assays. Although 
the investigator's noted the existence of such data during their oral responses to the 
RAC, the data has not been submitted. Therefore, approval of the protocol should be 
deferred. Dr. Post said that published studies demonstrate the effect of B7 on tumor 
immunogenicity and provide strong justification for the present human study. Dr. Miller 
agreed with Dr. Post's assessment. Dr. Chase stated that he is inclined to defer this 
protocol. Dr. Geiduschek said that he is in favor of approving this protocol on the basis 
that the preclinical data in question is not critical to support this proposal. Drs. 
Haselkom and Leventhal stated their concern that the RAC is employing a higher 
standard for this protocol than for previously approved studies; therefore, the protocol 
should be approved. Dr. Leventhal reminded the RAC that this protocol is a Phase I 
toxicity study; therefore, efficacy is not a primary objective. Dr. Straus said that the 
scientific background for this human trial is compelling and recommends approval. 
The motion to defer the protocol did not pass by a vote of 5 in favor, 12 opposed, and 1 
abstention. 
Committee Motion #2 
A motion was made by Dr. Post and seconded by Dr. Secundy to approve the protocol. 
Approval of the protocol is contingent on submission of the following: (1) data obtained 
from ongoing in vitro human melanoma experiments (to be reviewed by Dr. Parkman, 
but approval not required), and (2) inclusion in the Informed Consent document of a 
request for autopsy, a description of long-term follow-up, and a statement explaining that 
the study is non-beneficial (review and approval to be done by Drs. Leventhal and 
Zallen). A friendly amendment was made by Dr. Parkman and accepted by Drs. Post 
and Secundy to require that the Informed Consent document be separated into a 
document for subjects receiving transduced cells and another document for subjects 
receiving untransduced cells. The motion to approve the protocol passed by a vote of 15 
in favor, 2 opposed, and 1 abstention. 
XV. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: PHASE I STUDY OF 
IMMUNOTHERAPY OF ADVANCED COLORECTAL CARCINOMA BY DIRECT 
GENE TRANSFER INTO HEPATIC METASTASES /DJL RUBIN 
Review-Dr. Doi 
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Recombinant DNA Research, Volume 18 
