Recombinant DNA Advisory Committee - 12/2-3/93 
patient eligibility criterion that limits the study to those patients who undergo treatment 
for their primary tumor (i.e., available tumor cryopreserved) at Sharp Memorial 
Hospital, San Diego, California. The motion to approve the protocol passed by a vote of 
14 in favor, 0 opposed, and 2 abstentions. 
X. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: INJECTION OF GLIOBLASTOMA 
PATIENTS WITH TUMOR CELLS GENETICALLY MODIFIED TO SECRETE 
INTERLEUKIN-2 ( IL-2 ): A PHASE I STUDY/DRS. SOBOL AND ROYSTON 
Review-Dr. Krogstad 
Dr. Walters called on Dr. Krogstad to present his primary review of the protocol 
submitted by Drs. Robert E. Sobol and Ivor Royston of the San Diego Regional Cancer 
Center, San Diego, California. Dr. Krogstad said that this Phase I study involves 
glioblastoma patients. The objectives of this study are to: (1) to evaluate the safety of 
subcutaneous immunization with irradiated autologous or allogeneic HLA-A2 (human 
leukocyte antigen-A2) positive glioblastoma cells modified to secret IL-2, (2) evaluate 
the efficacy of these immunizations on tumor growth, (3) induce cellular or humoral 
responses by this process, and (4) compare responses induced by autologous versus 
allogeneic tumor cells. The rationale for this study is based on published data 
demonstrating that the HLA-A2 locus is a dominant haplotype for tumor antigen 
presentation. The investigators propose that peripheral immunization with 11^2 
transduced allogeneic glioblastoma cells will induce immune responses that will cross the 
blood-brain barrier from the systemic circulation into the brain. The investigators cite a 
study by Mahaley, et. al., that suggests the prolonged survival of patients following such 
immunizations. However, this study is difficult to interpret because these patients 
underwent other forms of treatment simultaneously. 
Dr. Krogstad explained that the investigators propose to use the retrovirus vector, 
GlNaCvI2.23 (Genetic Therapy, Inc), with a human IL-2 cDNA insert. This construct 
has been previously approved by the RAC for other human gene transfer studies. He 
expressed concern that allocating patients to 2 arms of the study may complicate 
interpretation of the data. He questioned whether the state of the art technologies (e.g., 
MRI and CT (computerized tomography)) will accurately assess questions of treatment, 
toxicity, and efficacy. Since the basis for this proposed study is data derived from a 
single patient study, issues such as toxicity and efficacy may not be accurately addressed. 
However, useful information may be gained about the immunologic effects of the 
proposed experiment. 
Review— Dr. Chase 
Dr. Chase agreed that useful information may be obtained from the immunological 
studies; however, this proposal is based on dubious neuroradiology of a single patient 
who received other forms of treatment (e.g., chemotherapy and radiotherapy) 
immediately prior to and during the course of the gene transfer study. Neither scientific 
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Recombinant DNA Research, Volume 18 
