CAVATAK™ is an investigational cancer therapeutic being developed by Viralytics. Its proposed mode of action is to kill both local tumour cells and distant metastatic cells, by direct cytolysis and by inducing an immune response to tumour cells.
CAVATAK™ is a naturally occurring, genetically unaltered, virus which often causes no symptoms following natural infection of humans, but can induce mild upper respiratory symptoms similar to that of the common cold viruses. CAVATAK™ therapeutic action results through its interaction with the ICAM-1 receptor which is present in abundance on the surface of many cancer cells - both primary and metastatic. CAVATAK™ infects cells through specifically attaching to the ICAM-1 protein and then begins to replicate exponentially, causing the cells to lyse or rupture – this process is called oncolytic activity. Following oncolysis, tumour antigens are released from the cancer cells into the blood stream. This has been shown to stimulate the hosts immune system, generating antibodies to the tumour antigens and instigating a process of natural immunity to the cancer cells.
Mode of action of CAVATAK™
The postulated anti-cancer mechanisms of action of CAVATAK™ are displayed in the following diagram:
CAVATAK™ has two proposed mechanisms of action: the primary mode is the direct lysis of tumor cells expressing ICAM-1 protein and the secondary mode is the induction of an immune response to the tumour following the release of melanoma antigens following tumour cell lysis. Within the tumour microenvironment the presentation of antigens in combination with CAVATAK™ capsid and nonstructural protein may further stimulate host-generated anti-tumour immunity. Although neutralizing antibodies to CAVATAK™ are developed within the first 14 days of dosing, Viralytics believes that continued dosing after the development of these antibodies can further contribute to the therapeutic effect by continuing CAVATAK™-mediated oncolysis of newly generated tumor cells or cells escaping prior challenge and release of tumour cell antigens in the environment of a functioning immune system. Repeated dosing acts as a booster of the immune response against tumour cells infected with CAVATAK™. Subsequent release of immune-stimulatory tumour cell antigens is suggested to activate anti-tumour cytotoxic T cells.