Recombinant DNA Advisory Committee - 12/2-3/93 
expanded in the presence of 11^2 to yield a large population of antitumor effector T 
cells. The latter are reintroduced into patients with concurrent IL-2 administration. Dr. 
Chang reported a significant response to this procedure in renal cell carcinoma patients 
with a lesser response observed in melanoma patients. This gene transfer protocol is 
intended to address melanoma because of the decreased response to adoptive 
immunotherapy. 
Dr. Geiduschek explained that this proposal attempts to up-regulate the immunogenicity 
of patients' tumor cells through enhanced IL-4 expression by transduction with the 
GBAH4-18 retroviral vector. Fifteen patients with advanced melanoma will be entered 
into this protocol. The objectives of this study are to: (1) assess the feasibility of 
transducing patients' tumor cells with the IL-4 gene and assess toxicity, (2) evaluate 
antitumor efficacy and in vivo immunological responses, and (3) evaluate the 
immunological reactivity of activated lymph node cells in vitro. There have been 
disappointing results obtained from the murine studies; no significant improvement was 
observed with IL-4 expressing cells. Dr. Geiduschek posed the following questions. 
What is the rationale for using the chicken actin promoter for expression of the IL-4 
gene? Optimal and sustained IL-4 production has not been demonstrated using patient 
tumor cells. Is there in vitro data available that demonstrates the immunological 
reactivity of these transduced cells? Have any differences been observed between lymph 
node cells stimulated with untransduced tumor cells versus IL-4 transduced cells? 
Although the PI has responded to some of the concerns raised by the primary written 
review, the protocol is too premature to recommend approval. However, if the RAC 
does recommend approval of this protocol, there should be stipulations to address the 
technical shortcomings of the study. 
Review-Dr. Motulsky (presented by Dr. Geiduschek) 
Dr. Geiduschek summarized Dr. Motulsky's written comments. This approach has 
biologic plausibility and appears feasible. The treatment schema is complex and requires 
considerable manipulation of tumor cells, patient immunization, preparation of 
lymphocytes from lymph nodes, and 11^2 administration. Since the investigators have 
previously demonstrated success with an analogous non-gene therapy approach, this study 
is justified and could result in improved tumor therapy. The Informed Consent 
document is appropriate. Since there are no new risks associated with the gene 
manipulation aspects of this study, the protocol should be approved by the RAC. 
Review— Ms. Meyers 
Ms. Meyers' concerns focused primarily on the Informed Consent document. The 
investigators have adequately responded to initial concerns regarding the use of the term 
"tumor vaccine," recommendations for male/female contraception, and patients' 
responsibility for research-related costs; therefore, the revised Informed Consent 
document is acceptable. 
Investigator's Responses-Drs. Chang and Kraus 
Recombinant DNA Research, Volume 18 
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