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Oncolytic viruses are therefore highly attractive agents to use in combination with cellular therapies when targeting solid tumours.].
Pre-clinical and clinical studies are currently evaluating the potential of oncolytic adenoviruses, herpesviruses, poxviruses, picornaviruses (including coxsackievirus, polioviruses and Seneca Valley virus), paramyxoviruses (including measles viruses and Newcastle disease virus (NDV)), reoviruses, parvoviruses and rhabdoviruses (e.g. The number of clinical trials evaluating OVs either alone or in combination with other therapies has expanded rapidly and these are summarised in detail in Table .
This review attempts to present opportunities to overcome these issues by highlighting potential for synergistic immunotherapy with oncolytic virotherapy.].
For a long time, it was assumed that the dominant mechanism underpinning the anti-cancer effect of these agents stemmed from their oncolytic potential.
The diversity of available OVs, each with their own hallmarks of tumour tropism and specificity, virulence and oncolytic potential allows for the nuanced and optimal selection of OVs for combined use with cellular therapies such as CAR T-cell therapy.
Furthermore, many OVs have undergone extensive iterative laboratory-based study during the development of anti-viral vaccines over many decades.
Many solid tumours present a significant barrier to this process whereby the TME is either non-permissive to entry of effector immune cells or exerts immunosuppressive effects on those cells that do manage to gain access .
The ability of recombinant OVs to modulate the TME is now being exploited further by rationally inserting transgenes to encode immunostimulatory cytokines, chemokines or co-stimulatory molecules into viral virulence genes, thus fulfilling a dual strategy of optimising tumour tropism and specificity.
This Review draws upon recent advances in the design of novel oncolytic viruses and CAR T-cells and provides a comprehensive overview of the synergistic potential of combination oncolytic virotherapy with CAR T-cell adoptive cell transfer for the management of solid tumours, drawing particular attention to the methods by which recombinant oncolytic viruses may augment CAR T-cell trafficking into the tumour microenvironment, mitigate or reverse local immunosuppression and enhance CAR T-cell effector function and persistence.These include its co-administration with immune checkpoint inhibitors targeted against programmed cell death protein 1 (PD-1; e.g.pembrolizumab or nivolumab), cytotoxic T lymphocyte antigen 4 (CTLA-4; e.g. Clinical use of CAR T-cell therapy on the other hand has emerged within the last decade.These provide immunological “danger signals” that include small molecules (e.g. By this means, OV infection results in enhanced tumour-associated antigen presentation (due to neo-antigen spreading), improved T-cell and natural killer (NK) cell trafficking into the tumour microenvironment (TME) and enhanced effector function, leading to a “bystander effect” at local and distant sites of disease.Efficacy of oncolytic virotherapy is therefore dependent upon a complex interplay between functional innate and adaptive immune cells within the patient and more specifically within the TME itself.