Recombinant DMA Advisory Committee - 6/9-10/94 
asked the following: (1) How is an anti-CEA immune response expected if there is 
immune tolerance to the same antigen? (2) Since CEA has a molecular weight of 
180,000 daltons and more than half of the mass is attributed to carbohydrate, are 
enzymes required to add the carbohydrate moiety to the CEA polypeptide? (3) Does 
antigen/antibody recognition require proper glycosylation of the CEA polypeptide? Dr. 
Haselkom said that the original submission was poorly written; however, the investigators 
have clarified previous concerns in their written responses. 
Review— Dr. Chase 
Dr. Chase said that the protocol involves intramuscular injection of a plasmid DNA 
encoding the CEA gene, and the proposed treatment does not carry the risks associated 
with retrovirus vectors. He objected to the use of the term "vaccine." The term 'Vaccine" 
has traditionally been used to describe immunization for the prevention of disease, not 
treatment of preexisting disease. He objected to the Informed Consent document 
statement that patients will be responsible for any costs of medical treatment required as 
a result of research-related injury. Subjects should be informed that no benefit is 
expected from participation in this study. The Informed Consent document should be 
revised to reflect these concerns. 
Review-Dr. Zallen 
Dr. Zallen stated that the investigators have provided complete responses to Section I-D, 
Informed Consent, of the Points to Consider. She noted concern about the statement 
regarding payment for research-related injuries that medical treatment "is not provided 
free of charge." The use of passive voice in this statement makes it unclear who will be 
billed. Will the financial responsibility imposed by this statement constitute a barrier to 
the participation in this study? She inquired whether animal studies have been 
conducted to determine if the plasmid DNA spreads beyond the original site of injection. 
Other Comments 
Dr. Walters noted written comments submitted by Ms. Meyers stating her objection to 
the use of the term "vaccine" throughout the Informed Consent document and the 
protocol. Ms. Meyers expressed concern regarding patients' responsibility for costs of 
medical tests and research-related injuries. Subjects should not be excluded from 
participation in this study based on their inabihty to pay for such costs. 
Ms. Buc commented that the statement in the Informed Consent document regarding 
compensation for research-related injuries does not exclude the patient's right to bring a 
lawsuit if such injuries resulted from negligence. Subjects have the right to choose to 
enter the protocol. Disclosure is the heart of Informed Consent; therefore, if the terms 
are clearly disclosed and agreed upon by the subject, the Informed Consent document is 
considered acceptable. Ms. Buc noted the inappropriateness of the RACs continued 
discussions on these Informed Consent issues. 
Recombinant DNA Research, Volume 19 
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