Oncolytic adenoviruses: a game changer approach in the battle between cancer and the immune system.

ABSTRACT

Introduction: Oncolytic adenoviruses are among the most studied oncolytic viruses because of their tumor selectivity, safety, and transgene-delivery capability. With a growing number of different immunotherapies against cancer, the extraordinary immunogenicity of the adenovirus has emerged as a differentiating strength. Enabling T-cell related therapies with oncolytic adenoviruses appears a promising approach due to its inherent ability to elicit responses from the adaptive immune compartment.

Areas covered: These viruses have successfully enhanced both adoptive T-cell therapies and immune-checkpoint therapies. Oncolytic viruses induce several effects at the tumor and on the systemic level that help to circumvent current limitations of T-cells and related therapies, such as T-cell trafficking, tumor immune suppressivity and antigen spreading.

Expert opinion: Taking into account the multitude of possibilities of treating cancer with immunotherapies, learning to optimize the combinations and administration strategies of these drugs, could lead to durable responses in patients with currently incurable cancers.

KEYWORDS:

• Immunovirotherapy
• oncolytic adenovirus
• viral vectors
• adoptive-cell transfer
• CAR T cell therapy
• TCR gene therapy
• checkpoint inhibitors
• immunotherapy

Article highlights

• After two decades of clinical experience and technical development, adenoviruses appear safe and effective therapies against cancer, but only one product has been approved heretofore.

• Oncolytic viruses can act as transgene delivery tools, achieving higher efficacy and lower toxicity than conventional delivery approaches.

• Oncolytic viruses trigger a series of immune-related processes that help to develop anti-tumor specific responses, while reducing immunosuppression.

• Due to adenovirus biology, oncolytic adenoviruses are interesting candidates to enable T-cell related therapies such as adoptive cell therapies or checkpoint inhibitors.

• Rational pairing and administration of immune therapies is needed to optimize treatment outcomes.

This box summarizes key points contained in the article.

Declaration of interest

A Hemminki is shareholder in Targovax ASA. A Hemminki is employee and shareholder in TILT Biotherapeutics Ltd. A Hemminki has consulted for Amgen. V Cervera-Carrascon and R Havunen are employees of TILT Biotherapeutics Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

Work on this paper was supported by Jane and Aatos Erkko Foundation, HUCH Research Funds (EVO), Sigrid Juselius Foundation, Finnish Cancer Organizations, University of Helsinki, TILT Biotherapeutics Ltd, European Commission Marie Curie Innovative Training Network (ITN) grant VIRION (H2020-MSCA-ITN-2014 project number 643130), and by University of Helsinki Doctoral Programme in Clinical Research.