PROSTVAC™ Treatment Hypothesis
PROSTVAC™ has been developed based on the hypothesis that
immunotherapies can harness the immune system to fight cancer. It
works by inducing a specific, targeted immune response that attacks
the cancerous prostate cells.
Initial efforts to develop an immune-mediated treatment for
patients with prostate cancer included the study of Poxvirus
vaccination. Advantages of the Poxviral vectors include the large
size of the genomes, which have allowed transgenes to be expressed
in a Vaccinia virus vector, as well as greater immunogenicity of
expressed proteins compared to native protein, attributed to the
inflammatory response triggered against highly immunogenic viral
proteins.
PROSTVAC™ works by stimulating an immune response against
tumors through multiple mechanisms:
- PROSTVAC™ targets a unique cancer cell antigen, i.e. PSA,
rarely present on normal cells. PSA can be found circulating in the
blood, as well as on prostate cancer cells. PSA generally is
present in small amounts in men who do not have cancer, but the
quantity of PSA generally rises as prostate cancer develops. The
higher a man's PSA level is, the more likely it is that cancer is
present, but there are many other possible reasons for an elevated
PSA level.
- PROSTVAC™ uses a tumor-associated antigen which is more
immunogenic, or more likely to cause an immune response, because
Bavarian Nordic altered its amino acid structure slightly.
PROSTVAC™ has encoded a PSA sequence which has a single
alteration in HLA-A2 epitope at position 155.
Poxviruses efficiently infect a wide range of host cells and
confer high level gene expression of transgenic PSA. The inclusion
of TRICOM further increases immunogenicity of vaccination, where
increases in number and particularly avidity of T-cell responses
have been shown.
