CLINICAL PROTOCOL 
Product: VCL-1102 
July 7, 1994 
VICAL INC. 
9373 Towne Centre Dr., Ste. 100 
San Diego, CA 92121 
through evolution of successively less immunogenic clones (20). Deficient 
expression of class I MHC molecules is one of the factors that limits the 
ability of tumor cells to present antigens to cytotoxic T cells. Freshly 
isolated cells from naturally occurring tumors frequently lack class I MHC 
antigen completely or show decreased expression (21-25). Reduced class I 
MHC expression could also facilitate growth of these tumors when 
transplanted into syngeneic recipients. Several tumor cell lines which 
exhibit low levels of class I MHC proteins become less oncogenic when 
expression vectors encoding the relevant class I MHC antigen are 
introduced into them (26-30). In some experiments, tumor cells which 
express a class I MHC gene confer immunity in naive recipients against 
the parental tumor (27-28). The absolute level of class I MHC expression 
however, is not the only factor which influences the tumorigenicity or 
immunogenicity of tumor cells. In one study, mouse mammary 
adenocarcinoma cells, treated with 5-azacytidine and selected for elevated 
levels of class I MHC expression did not display altered tumorigenicity 
compared to the parent line (31). 
The immune response to tumor cells can be stimulated by systemic 
administration of IL-2 (32), or IL-2 with LAK cells (33, 34). Clinical trials 
using tumor infiltrating lymphocytes are also in progress and responses 
have been noted (35). Recently, several studies have examined the tumor 
suppressive effect of lymphokine production by genetically altered tumor 
cells. The introduction of tumor cells transfected with an IL-2 expression 
vector into syngeneic mice stimulated an MHC class I restricted cytolytic 
T lymphocyte response which protected against subsequent rechallenge 
with the parental tumor cell line (7). Expression of IL-4 by plasmacytoma 
or mammary adenocarcinoma cells induced a potent antitumor effect 
mediated by infiltration of eosinophils and macrophages (36). These 
studies demonstrate that cytokines, expressed at high local concentrations, 
are effective antitumor agents. 
1.1 Direct Gene Transfer and Modulation of the Immune System 
The utilization of catheter-based gene delivery in vivo provided a model 
system for the introduction of recombinant gene-specific sites in vivo. 
Early studies focused on the demonstration that specific reporter genes 
could t^e expressed in vivo (37, 38). Subsequent studies were designed to 
determine whether specific biologic responses could be induced at sites of 
recombinant gene transfer. To address this question, a highly 
immunogenic molecule, a foreign major histocompatibility complex 
(MHC), was used to elicit an immune response in the iliofemoral artery 
using a porcine model. The human HLA-B7 gene was introduced using 
Recombinant DNA Research, Volume 20 
[ 601 ] 
