Anti-tumor immune responses following neoadjuvant immunotherapy with a recombinant adenovirus expressing HSP72 to rodent tumors.

Gene modification of tumor cells is commonly utilized in various strategies of immunotherapy preventive both as treatment and a means to modify tumor growth. Gene transfer prior to surgery as neoadjuvant therapy has not been studied systematically. We addressed, whether direct intra-tumoral injection of a recombinant adenovirus expressing the immunomodulatory molecule, heat shock protein 72 (ADHSP72), administered prior to surgery could result in sustainable anti-tumor immune responses capable of affecting tumor progression and survival in a number of different murine and rat tumor models.

Tumor immunity and prolonged survival following combined adenovirus-HSP72 and CEA-plasmid vaccination.

We have studied the effects of recombinant adenoviruses as immune adjuvants for DNA vaccination. In a mouse model, using the weak immunogen carcinoembryonic antigen (CEA), anti-CEA IgG production was significantly higher and occurred earlier when immunization included a recombinant adenovirus together with CEA-plasmid DNA. Combined immunization with a recombinant adenovirus expressing the immunomodulatory molecule heat shock protein 72 (ADHSP72) and CEA-plasmid DNA resulted in CEA-specific T-cell activation capable of protecting mice from tumor formation with CEA expressing cells.

Heat shock protein 72 expression allows permissive replication of oncolytic adenovirus dl1520 (ONYX-015) in rat glioblastoma cells.

In this study we have made novel observations with regards to potentiation of the tumoricidal activity of the oncolytic adenovirus, dl1520 (ONYX-015) in rat glioblastoma cell lines expressing heat shock protein 72 (HSP72) due to permissive virus replication. ONYX-015 is a conditionally replicating adenovirus that is deleted for the E1B 55 kDA gene product whose normal function is to interact with cell-cycle regulatory proteins to permit virus replication. However, many murine and rodent cell lines are not permissive for adenovirus replication.

Olivocerebellar projections are necessary for exogenous trophic factors to delay heredo-Purkinje cell degeneration.

The temporally protracted heredodegeneration of cerebellar Purkinje cells in shaker mutant rats can be modified: ablation of the inferior olive accelerates their degeneration whereas chronic intraventricular infusion of trophic factors extends their survival. The present study sought to determine if chronic trophic factor infusion could block the accelerated degeneration of Purkinje cells due to inferior olivary chemoablation thereby focusing on possible mechanisms for the amelioration of heredo-Purkinje cell death. When the inferior olive was chemically ablated with 3-acetylpyridine at the midpoint of 2 weeks of conjoint intraventricular infusion of glial cell line-derived trophic factor (GDNF) and insulin like growth factor type I (IGF-1) Purkinje cells were not protected by the exogenous trophic factors, but rather degenerated prematurely consistent with chemoablation alone.