Recombinant DMA Advisory Committee - 6/9-10/94 
GENE TRANSFER PROTOCOL ENTITLED: A PHASE I TESTING OF 
GENETICALLY ENGINEERED INTERLEUKIN-7 MELANOMA VACCINES /DRS. 
ECONOMOU, GLASPY, AND McBRIDE 
Review-Dr. Motulsl^ 
Dr. Walters called on Dr. Motulsky to present his primary review of the protocol 
submitted by Drs. James Economou, John Glaspy, and William McBride of the 
University of California, Los Angeles, California. This proposal is an open label, Phase I 
clinical trial to evaluate the safety and immunological effects of administering ILrl 
producing allogeneic and autologous melanoma cells to patients with metastatic 
melanoma. Three groups of 5 patients will receive 1 x 10^ irradiated, unmodified 
autologous tumor cells mixed with increasing numbers of IL-7 transduced allogeneic 
melanoma cells (M24 cell line). The number of transduced cells will be adjusted to 
produce increasing doses of IL-7 between 10 and 1,000 ng/24 hours. The vaccine will be 
administered as 3 biweekly subcutaneous inoculations. The study design will allow a 
dose-escalation evaluation of local and systemic toxicity. A final group of 10 patients will 
receive 3 biweekly inoculations of their autologous melanoma cells transduced with an 
11^7 retrovirus vector. Antitumor immunity will be measured by tumor cell skin tests, 
tumor biopsies, generation of specific antibodies for autologous tumor and M24 cells, 
and generations of cytotoxic T lymphocyte (CTL) precursors. 
Dr. Motulsky noted that this is the first proposal involving the IL-7 transgene in human 
subjects. The investigators have submitted both in vivo and in vitro experiments 
demonstrating an antitumor effect against melanoma cells. Data indicates stable 
cytokine expression and induction of CTL in nuxed lymphocyte tumor cell cultures. The 
investigators are currently conducting similar studies using the IL-2 transgene; therefore, 
they possess sufficient expertise to conduct the study. The retrovirus vector will be 
produced and tested by Targeted Genetics, Inc., Seattle, Washington. 
Review-Dr. Doi 
Dr. Doi asked the following questions: (1) Has the IL-7 transduced M24 cell bank been 
certified by the FDA? (2) Have rodent and monkey experiments been conducted to 
determine IL-7 toxicity? (3) The doses of IL-7 to be administered to patients are 10, 
100, and 1,000 ng/24 hr. Since the maximum obtainable level of IL-7 production is 10 
ng IL-7/1 X 10^ cells/24 hr, 1 x 10® transduced M24 cells would have to be administered 
to achieve the highest dose in addition to the autologous cells. Is this large number of 
cells feasible? (4) Have high dose 11^7 producer cells been successfully cloned? (5) 
Should the HSV-TK gene be deleted from the vector construct to prevent possible 
complications? (6) Is quantitative data available demonstrating the superiority of YLrl 
over 11^2, IL-3, IU6, and tumor necrosis factor? 
Review-Ms. Meyers (presented by Dr. Walters) 
Ms. Meyers raised three issues of concern in her written comments: (1) the use of the 
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