Table of Contents 
I. Abstract 3-4 
A Scientific Abstract 3 
B. Non-Technical Abstract 3-4 
II. Background . 4-12 
A. Clinical Aspects of Malignant Brain Tumors 4-5 
B Preclinical Studies 5-12 
1 . The Use of HSV TK with Ganciclovir In Cancer Models 5-7 
2 Toxicity of Ganciclovir 7 
3 The Clinical Spectrum of Wild-Type Adenovirus 
Infections of the CNS 7 
4 Experimentally Induced Wild-Type Adenovirus Infections 
of the CNS in Primates. 7-8 
5 Recombinant Adenovirus-Mediated Gene Transfer in Murine CNS 8 
6 Adenovirus-Mediated Gene Transfer in Non-Human Primate CNS 8 
7 Adenovirus-Mediated TK Gene Transfer in Rats with CNS Tumors 9 
8 Adenovirus-Mediated TKinase Gene Transfer in a Human Brain 
Tumor Xenograft Animal Model. 9-11 
9 Recombinant Adenovirus Vectors in Human Gene Therapy Trials. 12 
III. Clinical Design 12-19 
A Summary 12-13 
B Study Design 13-15 
1 Patient Eligibilty 1 3 
l.a Patient Selection 13 
l.b Screening evaluation 13 
2 Imaging Studies 13-14 
3 Clinical Trial 14-15 
C Evaluation for Safety 15-16 
1 Neurologic and surgical risk. 1 5 
2 Virus Infection 1 5 
3 Ganciclovir Toxicity 1 5 
4 Dose escalation 1 5 
5 Evaluation for dissemination of virus 1 6 
6 Dose limiting toxicity: Definition 1 6 
D Evaluation for Biological Efficacy 16-18 
1 Radiological evaluation. 16-17 
2 Positron emmision tomography (PET) evaluation. 1 7 
3 Pathologic evaluation 1 8 
E Evaluation for Immunological Response 18-19 
F Ethics Advisory Board 1 9 
IV. Isolation and Production of H5.010RSV7K Adenovirus 19-20 
A Construction of recombinant adenoviral vector-H5.010RSVTK' 1 9 
B Generation of Recombinant HS.OIORSVTX Virus 1 9-20 
C Sequence Analysis of Recombinant Virus, H5.010RSVTK 2 0 
D Strategy for Characterization of Clinical Grade Adenovirus - Quality 2 0 
Assurance and Control 
V. References 21-24 
Recombinant DNA Research, Volume 20 [351] 
