H101,
H102
and H103
are genetically
modified adenoviruses; each of them has an
E1B-55kDa deletion in their viral genome.
The E1B-55kDa gene is needed for the virus to effectively
replicate in cells. The 55kDa protein
can degrade p53
to prevent apoptosis of infected cells. As a result,
viruses carrying the E1B-55kDa gene deletion will only
replicate in tumor cells with mutated p53 or deficient
p53 pathway but not in normal human cells. These adenoviruses
are ideal target agents for treating multiple types
of solid tumors. In addition to the E1B-55kDa deletion,
viruses of the H100 series (H101,
H102
and H103)
have additional gene deletions in the E3 region, which
aims to increase the efficacy of oncolytic virus therapy.
The oncolytic adenovirus therapy developed by Sunway
Biotech Co.,Ltd is described in the following. First
a genetically
modified adenovirus is injected into the
tumor to infect and lyse the tumor cells as it has already
been said. Then, after the injection, some H101
patients run a fever that can induce the production
of Heat
Shock Protein (HSP). The heat shock protein
work as chaperons and facilitate the inducing of tumor-specific
cytotoxicity
lymphocytes (CTL). Sunway Biotech Co.,Ltd
preliminary results indicate that an external heating
of the tumor can also initiate thermally-induced HSP
synthesis.
On their side, all the H103
patients produce heat shock proteins after their injection
because of an insertion of the HSP70 gene into their
adenoviral genome.
This enhances the adenovirus anti-tumor effectiveness.
This enhancement of the HSP-mediated cytotoxic
response is especially important for metastatic
disease as it provides a way for killing tumor cells
distant from the site of viral injection .
With the therapy, you effectively control the local
regional tumor through direct adenovirus-induced cell
death but you also may induce a tumor-specific immune
response for killing tumor cells at metastatic
sites. |
