Oncolytics Biotech Inc T.ONC

may 3rd published article

[spesestsemper]

IJMS | Free Full-Text | OV Modulators of the Paediatric Brain TIME: Current Status, Combination Strategies, Limitations and Future Directions (mdpi.com)

Pelareorep is an oncolytic RV which had shown preclinical efficacy in immunocompetent glioma models after intravenous injection when combined with preconditioning with granulocyte-macrophage colony-stimulating factor (GM-CSF), which recruits APCs to the TIME [62]. In a phase 1 trial of Pelareorep in paediatric patients with recurrent or refractory high-grade brain tumours led to a MOS of 11.7 months with increased levels of monocytes observed in 60% of patients post-treatment [17]. Moreover, all patients showed drops in white blood cells, platelets and neutrophils in the first week after therapy, which recovered in week two [17]. Serum cytokine levels showed no significant differences between patients and it is unclear whether these findings were the result of preconditioning with GM-CSF or the treatment with pelareorep [17]. The findings of this study, however, were rather limited by the level of pretreatment and prognostic uncertainty of the included patient cohort, as well as the fact that only serum samples were taken for assessment of immune response [17].

In the paediatric clinical trials described above, OV treatment was related mainly to Grades 1, 2 and in some rare cases Grade 3 AEs and with 1 Grade 4 case (pelareorep) and thus did not lead to any serious neurological deterioration and decline of quality of life (QoL) by the time the clinical trials concluded [15,16,17,18]. However, most OV clinical trials do not have data available on QoL, neurological changes or long-term effects from long-term survivors due to how recently those trials were initiated, and future clinical trials on OVs should accommodate for this.

In light of these observations, these clinical trials suggest that oncolytic viruses may modulate the TIME by increasing immune cell infiltration, particularly of CD4+ and CD8+ T cells. Especially in these cases where immune modulation was successful, the survival benefit was significant. However, further research is needed to better understand the specific mechanisms involved and to determine whether these effects are primarily due to the viruses themselves or other factors such as pre-treatment interventions