Oncolytic Viruses Partner With T-Cell Therapy for Solid Tumor Treatment.

Amanda Rosewell Shaw,Masataka Suzuki

doi:10.3389/fimmu.2018.02103

Abstract

Adoptive T-cell immunotherapies, including chimeric antigen receptor-modified T-cells (CAR-T cells), have revolutionized cancer treatment, especially for hematologic malignancies. Clinical success of CAR-T cell monotherapy in solid tumors however, has been only modest. Oncolytic viruses provide direct cancer cell lysis, stimulate systemic immune responses, and have the capacity to provide therapeutic transgenes. Oncolytic virotherapy has shown great promise in many preclinical solid tumor models and the first oncolytic virus has been approved by the FDA for the treatment of advanced melanoma. As monotherapies for solid tumors, oncolytic virotherapy provides only moderate anti-tumor effects. However, due to their complementary modes of action, oncolytic virus and T-cell therapies can be combined to overcome the inherent limitations of each agent. This review focuses on the aspects of oncolytic viruses that enable them to synergize with adoptive T-cell immunotherapies to enhance anti-tumor effects for solid tumors.

Highlights

Clinical use of adoptive cell therapies to treat cancer has gained great interest in recent years, adding new treatment options to the paradigm of surgery, radiotherapy, and chemotherapy
It is well established that Oncolytic viruses (OVs) can stimulate adaptive immune responses to tumor cells due to the release of tumor associated antigens (TAAs), pathogenassociated molecular patterns (PAMPS), and danger-associated molecular patters (DAMPS) from lysed tumor cells
We generated a single vector expressing IL-12p70 with the PD-L1 blocking antibody which was co-injected with an oncolytic adenoviral vector (CAdVECIL12_PDL1). This treatment combined with Human epidermal growth factor 2 (HER2).chimeric antigen receptor (CAR)-T cells was able to control both primary and metastasized tumors in an orthotopic model of head-and-neck squamous cell carcinoma (HNSCC) causing lymph node metastasis similar to those seen in HNSCC patients

Summary

INTRODUCTION

Clinical use of adoptive cell therapies to treat cancer has gained great interest in recent years, adding new treatment options to the paradigm of surgery, radiotherapy, and chemotherapy. Combination Viro and T-Cell Immunotherapies stimulatory molecules and is abundant with inhibitory checkpoint molecules, and physical barriers of the solid tumor mass [6] (Figure 1A) These preclinical and clinical trials suggest that CAR-T cells are insufficient to overcome these inhibitory mechanisms as a monotherapy and require additional therapy to enhance their anti-tumor effect. It is well established that OVs can stimulate adaptive immune responses to tumor cells due to the release of tumor associated antigens (TAAs), pathogenassociated molecular patterns (PAMPS), and danger-associated molecular patters (DAMPS) from lysed tumor cells. Combining T-VEC with immune checkpoint inhibition provides complementary immune stimulation mechanisms as demonstrated in recent case studies [9,10,11] These clinical results clearly indicate that combination of OVs with another immunotherapy agent has additive anti-tumor effects. This review will focus on recent developments and applications in OVs that have the potential to synergize with adoptive T-cell immunotherapy

COMBINATION OF OVS WITH ADOPTIVE T CELL THERAPY

OVs for T Cell Retargeting

OVs and Checkpoint Blockade

CAR endodomain

Findings

CONCLUSION