Recombinant DNA Advisory Committee - 06/1-2/92 
Other Comments 
Dr. Parkman stated that the significance of this protocol, besides the therapeutic benefits 
it may offer, is that it sets a potential precedent for the introduction of transduced 
murine cells, which are capable of producing vectors in vivo into humans. It is important 
for the RAC to realize the great potential impact of this protocol. 
Dr. D. Miller asked Dr. Parkman to identify the concerns he has about introducing 
murine cells into humans. What are the scientific issues? Dr. Parkman stated that one 
potential problem is the persistence of the producer cells. 
Dr. Leventhal said that the investigators state in the protocol that "retroviral vectors will 
only transfer genes into proliferating cells, and in the brains of these patients the only mitotic 
cells will be tumor cells". This statement is not accurate. What about glial cells? There 
is a concern about the surgically accessible group of patients. At the time of tumor 
resection, these patients will be exposed to the viral material. Following tumor resection, 
these patients will have a lesion which is exposed to this viral material. It is inaccurate 
to say that the tumor cells are the only dividing cells. The investigators need to address 
this point. 
Dr. Krogstad asked the investigators if they were aware of any data which existed 
relating to profound hypersensitivity responses to mouse cells. 
Mr. Barton noted that much of the discussion surrounded the initial ten patients who 
would be treated for malignant primary brain tumors. The protocol defines another 
treatment group who are patients with metastases. The investigators need to justify why 
this second group of patients was included in this protocol. 
Dr. Zallen inquired about any scientific advantage for performing stereotaxic surgery in 
the surgically accessible group of patients prior to the surgical resection of their tumor. 
She asked Dr. Oldfield about the risks associated with these dual procedures? 
Dr. Parkman stated that although these cells will be injected within the confines of the 
blood/brain barrier, there is the potential that some of these cells may enter the systemic 
circulation due to surgical manipulation. This raises the possibility that these cells could 
enter the patient's germ line. The RAC should consider the fact that the in vivo 
introduction of these cells increases this probability. 
Dr. D. Miller asked the investigators to respond to his concern that the producer cell 
line that was used for the animal experiments is not the same cell line that is being 
proposed for use in humans. Have the PAT 2.4 cells been tested in an animal model? 
Recombinant DNA Research, Volume 15 
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