UAB9405 
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level. Rules for need to expand patient accrual at any particular dose level 
or stop progression to the next dose level are described in section 7.1 . 
6.5 Management of Adverse Drug Reaction (also refer to section 5.5) 
6.5.1 Acute Adverse Reaction to Polynucleotide Vaccine 
Administration 
To date, no serious or even mild acute toxicities from 
polynucleotide vaccines have been seen in mice (25), rats (27), 
ferrets (36), or non-human primates (36). In our own research, 
over 100 mice have received intramuscular injections into the 
tongue on multiple occasions (up to 1 8 times/mouse) with doses of 
0.01 to 0.25 mg without any evidence of subsequent pain, swelling 
or interference with grooming, eating or drinking. 
Patients will be monitored for any local signs of inflammation and 
may receive local heat application and transient anti-inflammatory 
agents if symptomatic. 
6.5.2 Late Toxicity 
No late toxicities have been associated with polynucleotide 
immunization in preclinical studies. It is conceivable that the local 
expression of a protein with associated immune response could 
cause local inflammation and muscle fiber damage. This has not 
been seen to date and preclinical studies suggest that only a very 
few fibers actually express antigen so that their destruction would 
not be clinically significant. No toxicity was noted in mice 
receiving a polynucleotide vaccine of HBsAg despite a brisk 
immune response. The potential for CEA synthesis and release 
should have no adverse effects given that these patients will have 
metastatic colorectal cancer with varying amounts of CEA already 
present. Immune response to CEA could produce anti-tumor 
effects while reactivity to cross-reacting family members of CEA 
family could induce neutropenia, colitis, hepatitis, or other organ 
dysfunction. Such events have not been seen in preclinical studies 
in animals who have homologous CEA family members nor in 
humans (over 20) or non-human primates given recombinant 
vaccinia-CEA immunizations. Patients will be monitored for such 
adverse events and treated appropriately. 
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Recombinant DNA Research, Volume 19 
