Baja eficiencia de las células mononucleares de sangre periférica para transportar el rotavirus oncolítico TRUYO a las células tumorales
Year: 2026
Type: article
Abstract: Introduction. Oncolytic viruses exert direct antitumor effects and modulate systemic immunity, but intravenous delivery is hindered by rapid antiviral responses. Identifying circulating cells that stabilize, and transport viral particles may improve systemic distribution and therapeutic performance.Objective. To determine whether murine peripheral blood mononuclear cells (PBMCs) can carry the oncolytic rotavirus TRUYO and deliver it to tumor cells after intravenous administration.Materials and methods. TRUYO infection of PBMCs was assessed after viral preincubation with protamine. Infection kinetics were analyzed at multiple time points and compared with virus alone. PBMCs loaded with the TRUYO–protamine complex were cocultured with adherent U937 (U937/A) tumor cells to evaluate viral transfer. The complex was then injected intravenously into Balb/c mice bearing SP2/O allogeneic tumors. Viral infection and cytostatic effects were examined via immunocytochemistry, immunofluorescence, and ELISA.Results. PBMCs showed minimal susceptibility to TRUYO immediately after isolation, but infection increased after 48 hours of culture, coinciding with surface heat-shock protein expression. Protamine markedly enhanced PBMC infection at 10 hours, an effect further potentiated by heat-shock conditioning. PBMCs carrying the TRUYO–protamine complex produced only a modest increase in U937/A infection in vitro. In vivo, intravenous administration resulted in limited tumor infection and negligible cytostatic activity.Conclusion. TRUYO infects PBMCs only when preincubated with protamine or under stress conditions, yielding infection levels proportional to the MOI. However, systemic administration of PBMCs loaded with TRUYO–protamine resulted in minimal tumor targeting. Optimizing PBMC conditioning and enhancing directed migration will be essential to improve this delivery strategy.
Source: Biomédica
Authors: Bedoya, Angie, Guerrero, Carlos Arturo
Institution: Universidad Nacional de Colombia
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: diamond
Funder: Universidad Nacional de Colombia
OpenAlex ID: W7212092261