Prospects for combined use of oncolytic viruses and CAR T-cells

Abstract

With the approval of talimogene laherparepvec (T-VEC) for inoperable locally advanced or metastatic malignant melanoma in the USA and Europe, oncolytic virotherapy is now emerging as a viable therapeutic option for cancer patients. In parallel, following the favourable results of several clinical trials, adoptive cell transfer using chimeric antigen receptor (CAR)-redirected T-cells is anticipated to enter routine clinical practice for the management of chemotherapy-refractory B-cell malignancies. However, CAR T-cell therapy for patients with advanced solid tumours has proved far less successful. 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.

oHSV2 Can Target Murine Colon Carcinoma by Altering the Immune Status of the Tumor Microenvironment and Inducing Antitumor Immunity

“…For example, arming viruses with immunostimulatory molecules would allow them to more effectively stimulate the immune system to produce longterm antitumor effects; 39,40 combining these viruses with traditional and novel approaches is a new research trend. 41,42 Cancer virotherapy has broad application prospects. However, improving the regulation of the balance between antitumor and antiviral activities remains challenging and requires further exploration.…”

Reversal of pure red cell aplasia by varicella zoster virus infection

“…Viruses have two opposing faces: (1) on the one side, they can cause harm and disease with early as well as late complications that carry signi icant morbidity and mortality and on rare occasions cellular transformation and cancer, and (2) on the other hand, viruses may provide hope to effectively treat several serious diseases [61]. Examples of the usefulness of certain viruses in the treatment of certain diseases include: use of viruses as vaccines; use of genetically engineered or naturally occurring viruses as anticancer agents in the setting of oncolytic virus therapy; and use of viruses as vectors in: induced pluripotent stem cells, gene therapy as well as chimeric antigen receptor T-cell therapy [61][62][63][64].…”

Delivery and Biosafety of Oncolytic Virotherapy

“…At the same time, the CAR-T antitumor effect on metastatic tumor sites overcomes the limitations of the oncolytic virus. The combination of these two approaches enhances the antitumor activity and has great application prospects (29,30). Oncolytic viruses combined with chemotherapy have shown a promising effect.…”