15 
protein. Resting or memory lymphocytes do not express IL-2 receptors. There 
is no evidence of IL-2 receptors on tissues outside of the lymphoid compartment. 
Or. Williams said the goal of this project is to selectively remove activated 
T cells and activated R cells during a well controlled time period following 
organ transplantation. It is hoped the IL-2-diphtheria toxin molecule would 
he more selective than the immunosuppressive techniques currently in use. 
Experiments in mice using anti-IL-2 receptor-monoclonal antibody conjugates to 
suppress cells which cause rejection in cardiac transplants support this hypo- 
thesis. In these experiments, the life of the graft in mice was extended from 
ID-14 days to three months or more in 80 percent of the animals. 
Dr. Gill said the "worst case" scenario he could conjecture vould be that an 
animal's T cells and B cells would be eliminated by this hybrid protein. A 
long observation of test animals might be necessary before such an effect 
would be detected. Dr. Habig said a long observation period might also be 
necessary for animals treated wath the o-MSH-diphthena hybrid protein. 
Dr. Levine said the IL-2-dipihtheria toxin hybrid protein could be an important 
therapeutic agent, but it would be a new toxin and could be harmful. He sug- 
aested contairment be initially set at the BIA level. 
Dr. Martin said the largest BL4 facility at the Frederick Cancer Research 
Facility is run by NIAID. Any request by Dr. Mirphy for use of the facility 
will need to be considers! by NIAID in relation to other competing requests. 
Dr. Levine said since little in known about the potential toxicity of the 
proposed hybrid protein, the working group approach should be conservative. 
If BI4 contairment is not available, the experiment should be permitted under 
' RL3 containment with a recognition that concern exists about the nature of the 
proposed hybrid protein. 
; Dr. Gottesman suggested contairment could be set at RL3 with a requirement for 
' the use of FK2 host-vector systems. Dr. Levine said he would accept the sug- 
j gestion to specify EK2 vectors ; he would not accept the suggestion to specify 
FK2 hosts . 
Dr. Gottesman asked whether any type of risk assessment ecperiment could be 
performed which would answer basic questions about the nature of the protein. 
Dr. Gill said risk assessment experiments with this hybrid protein would differ 
from previous risk assessment protocols because acute lethality is not a likely 
outcome. Tests would have to be devised to lock for chronic impairment of the 
immune system. This type of data and the protocols necessary to generate it 
are different from that generally required for toxins. 
Dr. Gill offered a motion to recommend permission to proceed under BL3 conditions; 
FK2 vectors would be used. Dr. levine said he would prefer the Language of 
the motion specified the use of "pcorly mobilizable plasmid vectors such as 
the FK2 certified plasmids." Dr. Gill agreed to this modification. Dr. Levine 
seconded the motion. 
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