Effect of preexisting immunity on oncolytic adenovirus vector INGN 007 antitumor efficacy in immunocompetent and immunosuppressed XXXX .

@entity5 @entity204 @entity786 @entity329
Immune responses against adenovirus (Ad) vectors pose a possible concern for the outcome of treatment efficacy. To address the role of preexisting immunity in oncolytic Ad vector antitumor efficacy following intratumoral injection of vector as well as @entity5 -to-tissue spread of the vector, we employed the @entity329 model. These animals are immunocompetent, and their @entity5 and tissues are permissive for replication of Ad type 5 (Ad5). We used the @entity204 protein-overexpressing Ad5-based vector INGN 007. @entity5 were established in groups of hamsters that were or were not immunized with Ad5. Half of the hamsters in these groups were immunosuppressed with @entity786 . For all groups, @entity5 injected with INGN 007 grew significantly more slowly than those injected with buffer. Under immunocompetent conditions, there was no significant effect of preexisting immunity on vector antitumor efficacy. Soon after the @entity5 in na  ve animals were injected with vector, the hamsters developed neutralizing antibody (NAb) and the difference in NAb titers between the na  ve and immunized groups diminished. Under immunosuppressed conditions, preexisting NAb did significantly reduce vector efficacy. Thus, NAb do reduce vector efficacy to some extent, but immunosuppression is required to observe the effect. Regarding vector toxicity, there was spillover of vector from the @entity5 to the liver and lungs in na  ve immunocompetent hamsters, and this was nearly eliminated in the immunized hamsters. Thus, preexisting immunity to Ad5 does not affect INGN 007 antitumor efficacy following intratumoral injection, but immunity prevents vector spillover from the @entity5 to the liver and lungs.
