Recombinant DNA Advisory Committee - 06/1-2/92 
indicates that it is extremely unlikely that an antibody response or cytotoxic response will 
be generated with an allogeneic cell alone, even if it expresses well established or 
characterized epitopes. 
Dr. Gansbacher addressed Dr. Kelley's question regarding the ability to analyze an anti- 
tumor response in a setting in which there will be a strong anti-allogeneic response. In 
essence, will there be enough autologous tumor cells available to test this response? Dr. 
Gansbacher stated that one possible option would be to remove lymphocytes from 
patients who only share the A 2 part of the allogenic vaccine and restimulate these 
lymphocytes with another allogeneic cell that shares only A2. This process will dilute out 
the in vivo anti-allogeneic response by restimulating with a cell which only presents A2, 
and possibly the shared peptide. Dr. Gansbacher described another possible approach 
using cold target inhibition assays in which the patient's lymphocytes will be assayed 
against the stimulated, autologous tumor cells. 
Dr. Parkman asked how A2 is going to be typed since there are sue or seven different 
subtypes? Have the investigators examined different isotypes of A2? Have the tumor 
cell lines been isotyped? Does the isotype affect the cell's capacity to present peptides 
to the T cells? 
Dr. Gansbacher responded that he is aware that eleven different allotypes of HLA-A2 
can be analyzed by DNA sequencing and five allotypes are distinguishable by 
immunoelectrofocusing. The patients will be matched with the vaccine cell line by 
allotype. 
In response to Dr. Kelley's question regarding the effect of pre-existing antibodies to IL- 
2, Dr. Gansbacher stated that if a primed population of cells already exists, the peak 
response of these cells will occur within 48 hours. If tumor cells are destroyed rapidly, a 
very strong immune response will be elicited in which proteins will be taken up and 
presented to incoming effector cells. Dr. Gansbacher said that if rapid destruction of 
tumor cells occurs, there may be enough remaining IL-2 secreted locally to start the 
cascade of antigen presentation and global amplification of the T cell clones that have 
the specific T cell receptor rearrangement. 
Dr. Parkman inquired if human complement is capable of mediating tumor cell lysis? If 
complement does lyse the tumor cells, the time frame will be less than 48 hours. Dr. 
Gansbacher answered that he has not performed these experiments; however, there is no 
evidence in the published literature that allogeneic vaccines have produced this effect. 
Dr. Gansbacher addressed the possibility that the vaccine may generate an autoimmune 
response to normal renal cells. In five different tumor models, there has never been any 
evidence of an autoimmune response. In particular, there is no indication that 
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