Recombinant DNA Advisory Committee - 06/7-8/93 
ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: A PHASE I TRIAL OF HUMAN GAMMA 
INTERFERON-TRANSDUCED AUTOLOGOUS TUMOR CELLS IN PATIENTS WITH 
DISSEMINATED MALIGNANT MELANOMA /DR. SEIGLER 
Review-Dr. Parkman 
Dr. Walters called on Dr. Parkman to present his primary review of the protocol 
resubmitted by Dr. Hilliard F. Seigler of Duke University Medical Center, Durham, 
North Carolina. This protocol was deferred at the March 1993 RAC meeting. Dr. 
Parkman briefly recapitulated the protocol. This Phase I trial will administer human 
gamma interferon (v-IFN)-transduced autologous tumor cells to patients with 
disseminated malignant melanoma. Autologous tumor cells will be grown in short-term 
culture and transduced with a vector expressing human y-IFN. If these cells express a 
minimal level of y-IFN, they will be irradiated with 10,000 rads and readministered to 
patients. The two endpoints to this study are: (1) clinical regression of tumors, and (2) 
the generation of cytotoxic T lymphocytes (CTL). Responding to previous concerns, the 
PI has provided data demonstrating that: (1) y-IFN transduced cells induce increased 
cytolytic activity in peripheral blood, (2) the cytolytic activity is due to CTL as well as 
natural killer (NK) cell activity, (3) production of y-IFN by transduced cells results in the 
up-regulation of Class I major histocompatibility (MHC) antigens, and (4) stimulation by 
transduced tumor cells results in increased CTL activity. Dr. Parkman stated that most 
of the scientific questions raised in the previous review have been addressed and 
recommended approval of the protocol. 
Review-Dr. Leventhal 
Dr. Leventhal stated that she was satisfied with the revised submission, and that the 
protocol should be approved in its present form. 
Review-Ms. Meyers 
Ms. Meyers raised a major concern about a statement in the Informed Consent 
document that requires patients to pay for any injury that occurs as a direct result of 
participation in the study. Dr. Carmen suggested minor changes to the Informed 
Consent document that would make the document more understandable to lay persons. 
Investigator Response-Dr. Seigler 
Dr. Seigler agreed to incorporate the minor changes in the Informed Consent document 
suggested by Dr. Carmen. In response to Ms. Meyers’ concern about patient 
compensation. Dr. Seigler said that immediate care is available for any individual who is 
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