Work

Transferrin-binding domain inserted-adenovirus hexon engineering enables systemic immune evasion and intratumoral T-cell activation

Year: 2024

Type: article

Abstract: Rationale: Adenovirus-based therapies have encountered significant challenges due to host immunity, particularly from pre-existing antibodies.Many trials have struggled to evade antibody response; however, the efficiency of these efforts was limited by the diversity of antibody Fv-region recognizing multiple amino acid sequences.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.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.

Source: Theranostics

DOI: 10.7150/thno.105163