Conclusion
This novel antibody-evading strategy effectively evades neutralizing antibodies and innate immunity while boosting cytotoxic immunity by recruiting CD8+ T cells at the tumor site. Additionally, this strategy holds potential for application in other gene therapies and adenovirus vectors.
Methods
In this study, we developed an antibody-evading adenovirus vector by encoding a plasma-rich protein transferrin-binding domain. The coding sequence was employed from Neisseria Meningitides and inserted in the experimentally-optimized site within the adenovirus capsid protein. Result: This engineered antibody-evading oncolytic adenovirus overcame the reduction in productivity and infectivity typically caused by the insertion of a foreign domain. We observed decreased immune recognition and compromised formation of anti-adenovirus antibodies. Furthermore, the anti-tumor efficacy was demonstrated both in vitro and in vivo, with increased recruitment of CD8+ T cells.