Recombinant DNA Advisory Committee- 9/12-13/94 
Dr. Eck said the question of inflammation will be examined from the brain tissues 
removed after vector administration, although it will be complicated by 
immunosuppression already existing in cancer patients. Dr. Parkman suggested in vitro 
systems of peripheral blood lymphocytes to observe for immune responses. Dr. Eck said it 
is included in the CTL assays they are planning to do. 
Regarding the question of prior immune status of the patients, Dr. Eck said that 
previously immunized patients have less chance of spreading the vector, but they may have 
more severe adverse reactions. 
Responding to Ms. Meyers concerns about duplication with other protocols, Dr. Eck said 
that it is a different vector and will have different toxicities. The knowledge about toxicity 
with this adenovirus vector will be useful. No additional surgical or lumbar puncture 
procedures are to be performed on these patients. All are standard procedures to treat 
brain tumors. So there is no undue stress on the family or the patients in proposing these 
procedures. 
Regarding the benefit section of the Informed Consent document, Dr. Eck agreed to the 
suggestion by Ms. Meyers and Mr. Capron to not imply any potential benefit to patients, 
but to mention potential societal benefit. 
Dr. James Wilson (University of Pennsylvania Medical Center) said that the most 
important scientific goal of these human studies of adenovirus vectors is to understand the 
interactions of host with this potentially therapeutic vehicle. An important aspect of these 
studies is to critically evaluate the immunological profiles of the recipients to adenoviruses 
before and after gene therapy. A series of serological tests for adenoviral antibodies and 
CTL assays will be used to assess the immunological responses. But how these in vitro 
assays correlate with clinical reactions is still unclear. Dr. Wilson agreed that enhanced 
inflammation in repeat administration is a concern, and he agreed to perform the 
experiments on pre-immunized animals suggested by Dr. Parkman. 
Addressing the vector question raised by Dr. H. Ginsberg, Dr. Wilson said he has finished 
sequencing the whole vector DNA. The partial deletion in the E3 region involves the 
deletion of the gene coding for the 14.7 kd protein, but the gene for the 19 kd protein is 
intact. The latter gene affects the level of class I major histocompatibility antigen 
expression. Dr. Wilson said that he has conducted experiments comparing side by side the 
E1-E3 deleted virus with the adenovirus deleted only at El. No significant difference in 
pathogenicity to the lung and the fiver has been observed. Dr. Miller asked what animal 
was used in this experiment. Dr. Wilson said it is a mouse experiment, and Dr. H. 
Ginsberg said it is a valid animal for this experiment. Dr. H. Ginsberg has conducted 
similar experiments in cotton rats but with wild-type virus and E3 deletion, he has 
observed some differences. Dr. Miller expressed concern about the interpretation of these 
somewhat conflicting results. He asked why any portions of the E3 region have to be 
deleted from the vector construct. Dr. Wilson said it is easier to clone the E3 deleted 
DNA because some troublesome restriction enzyme sites are removed. Dr. Wilson said 
this vector has the same El deletion as the one for CF, but it retains 2.5 kb of the E3 
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Recombinant DNA Research, Volume 20 
