Viral Based Therapies

Adenoviral vectors have been used to deliver angio-statin, an internal fragment of plasminogen containing the first four kringle structures fused to human serum albumin (K3-HAS) (Joseph et al. 2003). Mice bearing IGR-N835 neuroblastomas were administered 5x109 PFU (plaque forming units) by intravenous injection when tumors were either early stage, established, or at a state of minimal residual disease. No delay in tumor growth in animals treated with AdK3-HAS was observed compared with control empty virus. K3-HAS was found to be expressed at high levels; hence, it would appear that this approach may not be successful. Instead, IGR-N835 tumors were found to secrete high concentrations of VEGF suggesting that targeting this ligand or its receptor system may be more useful.

A novel approach to treatment of neuroblastoma has been to administer the avian paramyxovirus Newcastle disease virus either by direct intratumoral injection or by intraperitoneal injection (Phuangsab et al. 2001). After a single intraperitoneal injection of 5x109 PFU complete regression of IMR-32 neuroblastomas was observed in 9 of 12 mice without recur rence for 3-9 months. In half of those mice where tumor recurred complete response was achieved with three additional courses of treatment. Viral-dependent enzyme prodrug therapy (VDEPT) has also been used to selectively purge neuroblastoma-contami-nated human or murine bone marrow. Adenovirus encoding a carboxylesterase that efficiently activates the DNA topoisomerase-I poison irinotecan (CPT-11) was used to selectively activate drug in NB-1691 neuroblastoma cells. Purged marrows were bioas-sayed by injecting cells into SCID mice. Interestingly, marrows having up to 10 % tumor cells were successfully purged, as determined by loss of detection of neuroblastoma markers tyrosine hydroxylase and MYCN, and failure to establish disease in mice (Wagner et al. 2002).

0 0

Post a comment