CLINICAL PROTOCOL 
Product VCL-1102 
July 7, 1994 
VICAL INC. 
9373 Towne Centre Dr., Ste. 100 
San Diego, CA 92121 
1.0 Background and Rationale 
Immunotherapy has shown promise as an approach to the treatment of 
malignancy. The goal of immunotherapy is to stimulate the immune 
system to recognize and kill cancer cells. This is achieved either by 
modifying the tumor cells or the host response causing various 
lymphocyte populations particularly cytotoxic T lymphocytes, to respond 
specifically to tumor cell antigens. In fact, cancers such as melanoma, renal 
cell carcinoma and colon adenocarcinoma are responsive to 
immunotherapy because the immune system can be induced to recognize 
tumor associated and tumor specific antigens in these cells. 
In some instances, the immune system appears to contribute to.the 
surveillance and destruction of neoplastic cells, either by mobilization of 
cellular or humoral immune effectors. Cellular mediators of antitumor 
activity include MHC-restricted cytotoxic T cells (CTLs), natural killer 
(NK) cells (1, 2) and lymphokine-activated killer (LAK) cells (3). Cytolytic 
T cells which infiltrate tumors have been isolated and characterized (4). 
These tumor infiltrating lymphocytes (TIL) selectively lyse cells of the 
tumor from which they were derived (5, 6). Macrophages can also kill 
neoplastic cells through antibody-dependent mechanisms (7, 8), or by 
activation induced by substances such as Bacillus Calmette-Gu^rin BCG 
(9). 
Cytokines can also participate in the antitumor response, either by a direct 
action on cell growth or by activating cellular immunity. The cytostatic 
effects of tumor necrosis factor-a (TNF-a), interferon a (IFN-a), interferon 
y (EFN-y) (10) and lymphotoxin (11) can result in neoplastic cell death. 
Interferon-y markedly increases class I and II MHC cell surface expression 
(12, 13) and synergizes with TNF- a in producing this effect (14). Colony 
stimulating factors such as G-CSF and GM-CSF activate neutrophils and 
macrophages to lyse tumor cells directly (15), and Interleukin-2 (IL-2) 
actiyates Leu-19+ NK cells to generate lymphokine activated killer cells 
(LAK) capable of lysing autologous, syngeneic or allogeneic tumor cells 
but not normal cells (3, 16, 17). The LAK cells lyse tumor cells without 
preimmunization or MHC restriction (18). Interleukin-4 (IL-4) also 
generates LAK cells and acts synergistically with IL-2 in the generation of 
tumor specific killer cells (19). 
Since most malignancies arise in immunocompetent hosts, it is likely that 
tumor cells have evolved mechanisms to escape host defenses, perhaps 
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