Recombinant DNA Advisory Committee - 09/9-10/93 
recommending that AZT administration and rabbit pyrogen testing should not be 
mandatory, (2) the RAC will be notified of the name of the laboratory that will conduct 
RCR testing on the master cell bank and a detailed list of the tests that will be 
performed, and (3) the investigators will demonstrate that they can perform the 
transduction procedure on a clinical scale using cells from HIV-infected patients. The 
motion passed by a vote of 17 in favor, 0 opposed and 1 abstention (Dr. Geiduschek 
abstained from voting because he is employed by the same institution). 
XII. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: GENETICALLY ENGINEERED 
AUTOLOGOUS TUMOR VACCINES PRODUCING INTERLEUKIN-2 FOR THE 
TREATMENT OF METASTATIC MELANOMA /HRS. ECONOMOU AND GLASPY 
Review-Dr. Motulsky 
Dr. Walters called on Dr. Motulsky to present his primary review of the protocol 
submitted by Drs. James S. Economou and John Glaspy of the University of California, 
Los Angeles, California. This protocol is a study of patients with metastatic melanoma 
who have failed standard therapy. In an attempt to increase the patient's immune 
response to the tumor, the IL-2 gene will be introduced into a human melanoma cell line 
(M-24). The gene-modified melanoma cell line producing EL-2 will then be mixed with 
tumor cells obtained from the patient. This mixture of cells will be lethally irradiated 
and injected subcutaneously into patients. This injection is expected to augment the 
immune response of the patients to tumor cells through the immune stimulatory effects 
of IL-2 secreted by the gene-modified cells. Animal models have shown that injection of 
gene-modified cells has important anti-tumor effects. To determine the safety of the 
procedure, a constant number of tumor cells will be mixed with escalating numbers of 
IU2 producing cells. The study will involve 30 patients in 3 dose-escalation groups. The 
following endpoints will be measured: (1) toxicity, (2) generation of CTL precursors, 
lymphokine activated killer (LAX) cells and enhanced natural killer (NX) activity, (3) 
immunohistochemistry and delayed-type hypersensitivity skin tests using injection of 
irradiated autologous tumor cells, and (4) clinical anti-tumor responses. Dr. Motulsky 
stated that most of his initial concerns have been adequately addressed by the 
investigators. Several questions remain: Have experiments been performed in which IU 
2 is injected locally to observe any effect on tumor growth? What is the rationale of 
mixing the allogeneic M24 cells in the vaccine cocktail? Would other IL-2 producing 
cells, such as transduced B-lymphocytes, serve the same purpose? Will HLA typing of 
autologous and allogeneic cells be performed? 
Dr. Motulsky provided the following comments in regard to the Informed Consent 
document: (1) abbreviations should be avoided since they may not be understood by 
laypersons, (2) the use of the term "vaccine" is inappropriate and misleading, (3) the 
statement that describes the patient's consent as "received" should be more appropriately 
be described as "given", (4) the issue of financial risk to patients for costs associated with 
an investigational procedure should be addressed, and (5) the statement that addresses 
the commercial value of cell lines should be clarified. The investigators should provide 
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