Treatment of unresectable metastases remains a challenge in oncology. In special because the abscopal effect remains limited in the clinic mainly due to the suppressive microenvironment surrounding cancer cells. The systemic use of immune checkpoint inhibitors, such as anti- anti-PD-1 (anti programmed cell-death protein 1), has shown promise in the treatment of various tumour types, but only a minority of patients respond. Oncolytic virotherapy (OV) is an interesting strategy able to prime the host immune system against tumour epitopes to generate anti-tumour immunity. Then, theoretically complementing anti-PD-1 therapy in an appealing manner. The challenge with OV is that not all metastases can usually be injected. Therefore, it is important to study if local treatment can induce distant responses. While our previous work has shown synergy between oncolytic adenovirus and anti-PD-1, here we sought to establish if local adenovirus injection can impact also non-injected tumours in a pre-clinical model in the context of systemic anti-PD-1 therapy.
We engrafted melanoma mouse cells (B16.OVA) in both flanks of immunocompetent mice. Anti-PD-1 treatments were administered systemically, but only one tumour received local virotherapy with the non-replicative adenovirus. Progression was followed in both tumours and compared for possible systemic effects following local treatment, including immune responses.
Tumour growth control and overall survival were significantly better in non-injected tumours in the group receiving the anti-PD-1 plus virus, over monotherapy and control groups. In particular, treatment with anti-PD-1 plus virus was the only group that induced complete response of both tumours. Further information, including immunological mechanism-of-action data, will be presented.
TNFa and IL-2 armed adenovirus seems a promising approach to improve the efficacy of checkpoint blockade, and the effects can be seen in both injected and non-injected tumours. Here, the systemic anti-tumour effects result from local injection of the virus. A clinical trial is in progress (NCT04217473).
Legal entity responsible for the study
University of Helsinki.
Aatos Erkko Foundation, HUCH Research Funds (EVO), Finnish Cultural Foundation, Sigrid Juselius Foundation, Finnish Cancer Organizations, University of Helsinki, The Finnish Society of Sciences and Letters, and TILT Biotherapeutics Ltd.
R. Havunen: Full/Part-time employment: TILT Biotherapeutics. A. Hemminki: Shareholder/Stockholder/Stock options: TILT Biotherapeutics. All other authors have declared no conflicts of interest.