|
Based on historical evidence and in anticipation that control of
most tumors will rely on more than one therapeutic modality, we
have chosen to harvest the oncolytic potential of HSV1716 in combination
with standard treatments of e.g. chemotherapy and radiotherapy.
It is known that not all tumor cells are susceptible to a single
chemotherapy agent or to ionizing radiation. Combining chemo- and
radiotherapy with the oncolytic ability of HSV1716 will not only
result in an additive tumor killing effect but will also allow combination
treatments to be delivered as a single agent.
- HSV1716 + gene directed enzyme prodrug therapy
(GDEPT)
- HSV1716 + targeted radiation
- HSV1716 + antisense or siRNA
In addition to HSV1716 being used as an oncolytic therapy, the potential
of its use as a vector has to be considered. Although HSV1716 can
only replicate in dividing cells, it can infect a wide range of
non-dividing cells and deliver non-HSV gene products without damage
to the infected cell. The HSV genome has the ability to accommodate
up to 30kb of exogenous DNA and the virus is able to remain in a
latent/persistent state over a very long period of time.
Crusade is currently developing HSV1716 as a vector
in the treatment of non-malignant diseases, e.g. diabetes. Go
to HSV1716.com ->
Although HSV1716 has strong therapeutic potential for the treatment
of human malignancies, it will be essential to overcome cell-type
and mode of delivery restrictions in order to increase the efficiency
of infection.
To achieve tumor cell type targeting, we are modifying
the tropism of HSV. We have made a range of complexes comprising
HSV1716 and a targeting agent in the form of an antibody binding
domain. We have shown that these specific antibodies incorporated
into the viral envelope influence the tropism.
To develop a systemic delivery system that
avoids immunological detection and can specifically target tumor
cells, we have created ‘stealth’ viruses that can be
delivered intravenously.
|
