Recombinant DNA Advisory Committee - 03/1-2/93 
METASTATIC RENAL CELL CARCINOMA /DR. SIMONS 
Review-- Dr. Smith 
Dr. Walters called on Dr. Smith to present his primary review of the protocol submitted 
by Dr. Jonathan Simons of Johns Hopkins Oncology Center, Baltimore, Maryland. 
Dr. Smith provided a brief overview of the proposed study. This protocol is a Phase I 
vaccination study for the treatment of metastatic renal cell carcinoma for patients who 
have failed conventional therapy. Patients will receive transduced or untransduced cells 
in a randomized dose-escalation fashion. 
The investigators have submitted extensive data from an in vivo murine model. The 
rationale for this protocol is based on published scientific data demonstrating that 
granulocyte-macrophage colony stimulating factor (GM-CSF) significantly enhances 
tumor regression. Safety and tolerance of the vaccination procedure, as well as any 
adverse effects associated with gene transfer, will be critically evaluated. Long-term 
potential toxicity will also be monitored, i.e., autoimmune disease. In addition, the 
investigators will monitor immune response to the transduced and untransduced cells. 
The proposed retrovirus vector has a high efficiency of transduction and does not require 
selection. The patient's cells will be irradiated with a maximum dose of 15,000 rads. 
This dose of radiation does not adversely affect GM-CSF production, but inhibits tumor 
cell growth. Primary cell cultures will be used instead of long-term cell culture lines. 
Dr. Smith stated that his written comments to the investigators addressed their ability to 
evaluate immune responsiveness in these patients in the absence of clinical endpoints. 
The investigators provided adequate responses and explained that additional biopsies of 
the draining lymph nodes potentially will be taken and assayed for immune 
responsiveness. The investigators should describe the types of assays that will be 
performed on these biopsy specimens. Also, the investigators should provide additional 
data regarding the safety and design of the proposed vector. 
Review-Dr. Brinckerhoff 
Dr. Brinckerhoff stated that this protocol is very well designed and documented. The 
major concern is the investigators' ability to cultivate and grow the primary tumor cell 
cultures obtained from the patients' kidneys. Primary cell cultures are difficult to initiate 
and expand. The investigators responded that they have been successful in all except 
one attempt to develop these primary cell cultures. The investigators should comment 
on the ease with which they have been able to establish these cultures. 
Recombinant DNA Research, Volume 17 
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