Recombinant DNA Advisory Committee - 03/1-2/93 
Dr. Walters called on Dr. Miller to present his primary review of the protocol submitted 
by Drs. Peter A. Cassileth and Eckhard Podack of the University of Miami/Silvester 
Cancer Center, Miami, Florida. The objective of this protocol is to enhance localized 
cytokine secretion in order to stimulate an immune response against cancer cells. Tumor 
cells from patients with limited stage small-cell lung carcinoma (SCLC) will be 
transfected with a bovine papilloma virus (BPV) expression vector producing IL-2. 
Tumor cells expressing IU2 will be irradiated to reduce their replication potential and 
re-introduced into patients after chemotherapy-induced disease remission. Animal data 
generated by these investigators in the Lewis lung carcinoma model supports the concept 
that such manipulations can induce rejection of implanted IL-2-secreting tumor cells. 
The investigators have shown that they can grow SCLC cells from human patients, and 
that the cells produce relatively high levels of IL-2 after transfection with the BPV 
vector. 
Dr. Miller pointed out that this protocol is the first study designed to use a potentially 
oncogenic BPV vector as a vaccine. Sixty-nine percent of the BPV genome, including all 
early genes but not the late capsid genes, is included in the vector. These sequences 
include BPV genes with transforming potential. There is a concern whether the BPV 
vector is indeed replication-defective and that it does not pose any biohazard or 
possibility of spreading to other parts of the patient's body or to the population at large. 
The investigators have reviewed the previous literature and concluded that because of its 
size and lack of capsid proteins, the BPV vector is replication-defective. In his written 
review, Dr. Miller asked whether the BPV vector provides improved expression levels of 
cytokines in the human target cells over the standard retrovirus vectors that would 
clearly justify its use in humans. This question was not satisfactorily answered by the 
investigators. Also, there is a lack of convincing evidence in the animal model that 
injection of irradiated IL-2-secreting mouse tumor cells can promote rejection of existing 
tumor cells. 
Review-Dr. Secundy (presented by Dr. Dronamraju) 
In Dr. Secundy's absence, Dr. Walters called on Dr. Dronamraju to summarize her 
written comments. Dr. Secundy's concern was primarily with the informed consent 
document as follows: (1) the potential benefit statement appears too strong; (2) the 
financial responsibility of the institution in the event of unanticipated side effects of the 
treatment continues to be problematic, and (3) the question of unpredictable adverse 
consequences related to recombination of the vector with the human genetic material. 
In the revised consent form, the investigators addressed these concerns and included a 
statement about liability for costs of medical care engendered by side effects of therapy. 
Review-Dr. Dronamraju 
Recombinant DNA Research, Volume 17 
[125] 
