4.4.4 Corticosteroid therapy, local or systemic, for treatment of debilitating local or systemic immune 
reactions is permissible. 
5.0 REQUIRED OBSERVATIONS 
5.1 Clinical Assesment 
5.11 Pretreatment Evaluation 
5.11.1 History, physical examination, weight, vital signs, performance status; 
5.1 1.2 CBC, platelet count, AST, ALT, bilirubin, PT, PIT, urinalysis; 
5.11.3 Chest x-ray; 
5.1 1.4 Tumor measurement (CT, MRI or ultrasound). 
5.2 Evaluation During Treatment 
5.21 Weekly physical examination, vital signs, weight, performance status weeks 0-4 and then as indicated 
with a minimum of monthly evaluations; 
5.22 CBC, platelet count, AST, ALT, bilirubin, urinalysis before each tumor cell injection; 
5.23 Tumor measurement (CT, MRI or ultrasound) on weeks 8, 24, and 36. 
5 . 3 During Follow-Up; If the patient is on study after the week 36 injection, follow-up as below until 
the patient goes off study; 
5.31 Monthly physical examination, vital signs, weight, performance status x6 and then every three months 
for three years; 
5.32 Monthly CBC, platelet count, AST, ALT, bilirubin, PT, PTT, urinalysis x6 and then every three 
months for three years; 
5.33 Tumor measurement every three months x 4 and then every 6 months. 
6.0 DRUG INFORMATION 
6.1 Interferon-gamma transduced human neuroblastoma cells. Each cultured human 
neuroblastoma cell line is given an anonymous designation (CHLA-cell line number) and each IFN-y transduced line 
or subclone receives an additional EFN-y designation. Thus, for example, a transduced cell line could be designated 
as follows: CHLA-l(X)-IFN-3. This identifying data with appropriate descriptive and testing information will be 
maintained in a computerized database. 
6.11 Preparation of IFN-y Transduced Neuroblastoma Cells. Neuroblastoma cells from 
surgical, marrow, or blood specimens will be utilized to establish tumor cell lines. The resultant cell culture will be 
transduced with the IFN-y retroviral vector construct, which will be provided by Viagene, Inc. The transduced 
tumor cells will be evaluated for IFN-y, MHC class I and II, and B7 expression (See Appendix L). Cell lines (or 
subclones) that express class I antigens and IFN-y will be identified for clinical use and subjected to standard testing 
according to FDA and RAC guidelines, (see Tables 1-5, Appendix L). 
If possible, an autologous tumor cell vaccine will be prepared for each patient. However, if this is not possible, a 
single locus matched allogeneic tumor cell vaccine will be prepared. The relative frequencies of HLA-A and -B loci 
is not random, with unusually high representation of certain subtypes among different ethnic groups. As an 
example, over 49.4% of Caucasians, and 48.3 % of Asians, and 31.9% of Blacks express the HLA-A A2 antigen. 
Similarly, the HLA-B B44 antigen is seen in 23.0% of Caucasians, 11.6% of Asians and 14.8% of Blacks. 
Therefore, within our relatively large tumor bank (>100 cell lines), there may be a significant representation of 
certain HLA-A and -B subtypes, and even shared haplotypes may not be rare. Serologic (lymphocytes, bone marrow, 
neuroblastoma cells if HLA expressed) and genotypic (neuroblastoma cells) HLA typing will be done by Dr. P. 
Terasaki. Those tumors with frequently shared MHC class-I antigens (eg., A2, B3, B44) will be used to generate a 
library of IFN-y producing cell lines that express MHC molecules. This library will include N-myc amplified and 
non-amplified cell lines so that appropriate biologic subtypes are available for allogeneic immunization. Hence, if 
certain neuroblastomas have common MHC antigens, they could serve as a presenting source of tumor cell derived 
[ 102 ] 
Recombinant DNA Research, Volume 19 
