Table 1.
Oncolytic viruses as immunotherapeutics
| Type of immunotherapy | Phase of Study (tumor model) | Immune component(s) involved | Therapeutic outcome | References |
|---|---|---|---|---|
| OVs | ||||
| VSV | Preclinical (Melanoma) | CD8+ T cells or NK cells | No regression of B16Ova tumors in mice lacking CD8+ T cells and/or NK cells | [21] |
| Reovirus | Preclinical (Melanoma) | CTLs | Purging of B16Ova metastases from spleen and lymph node in immune-competent mice but not in SCID mice | [38] |
| NDV | Preclinical (Colon cancer) | PBMCs | Significant delay in growth of CT26 tumors | [39] |
| HSV | Preclinical (Sarcoma) | High baseline level of neutrophils was associated with sensitivity to OV; resistance to OV correlated to high baseline level of TAMs |
Formation of protective antitumor immunity leading to rejection of subsequent tumor challenges | [33] |
| Oncolytic adenovirus (Delta24-RGD) | Preclinical, (Glioma) | Local rapid release of acute-phase cytokines (including IL-1b and IL-6), interferon gamma (IFNγ), CXCL10, MIP-1α; tumor infiltration by macrophages and CD8 + T cells; | Induction of an anti-tumor memory response, which prevented tumor growth upon reinjection of tumor cells | [32] |
| HSV-2 (FusOn-H2) | Preclinical (Breast cancer) | T cells | Regression of primary and metastatic tumors | [35] |
| ICP34.5-deleted HSV | Preclinical (Melanoma) | Cytotoxic T cell response; CD4+ and NK cells also implicated | Prolonged survival of mice bearing intracranial melanomas | [36] |
| OVs armed with immune-stimulatory genes | ||||
| HSV-1 encoding GM-CSF | Preclinical | Induction of IFNγ, memory T cells | Regression of OV injected and noninjected tumors, resistance to re-challenge formation | [40] |
| OncovexGM-CSF or T-VEC | Phase I clinical trial (Melanoma) | TILs | Regression of injected and uninjected tumors | [47] |
| Phase II and III clinical trials (Melanoma) | Local and systemic antigen-specific T cell responses, and significantly reduced immune-suppressive cells (Tregs and MDSCs) | Anti-tumor activities in both injected and uninjected distant lesions | [48,49][50] | |
| Oncolytic vaccinia virus JX-594 encoding GM-CSF | Phase I clinical trial (Liver cancer) | Activation of systemic immunity | Regression of both injected and uninjected tumors | [16] |
| Oncolytic adenovirus encoding GM-CSF (ONCOS-102) | Phase I (Ovarian cancer) | Infiltration of CD8+ T cells in tumor; systemic induction of tumorspecific CD8+ T cells | Local and systemic anti-tumor immune responses | [51] |
| Combination therapy | ||||
| Oncolytic adenovirus with PD-1 inhibitor | Preclinical (Lung cancer) | Neoantigen-directed T cell response | Synergistic anti-tumor effect | [58] |
| Oncolytic VSV plus recombinant adenovirus vaccine boost | Preclinical (Melanoma) | CD8+ T cells, effector and memory | Combination produced a synergistic increase in numbers of both effector and memory CD8+ T cells | [34] |
| Adoptive T cell therapy plus oncolytic VSV | Preclinical (Melanoma) | CD8+ T cells, CCR7hi | Autologous CCR7hi T cells destroyed metastatic cells within lymph nodes, spleen and other organs | [37] |
| Oncolytic Adenovirus encoding CCL20/IL-15 + NK cells + CD8+ T cells | Preclinical (Colorectal cancer) | NK and CD8+ T cells-mediated cytotoxicity | Enhanced anti-tumor activity | [27] |
| Oncolytic HSV-1 + bortezomib + NK cells | Preclinical (Glioma) | Bortezomib sensitized oHSV infected tumor cells to NK cells | Synergistic anti-tumor effect | [28] |
| T-VEC plus anti-PD-1 antibody | Phase Ib trial (Metastatic melanoma) | T cell infiltration into tumors | T-VEC increased efficacy of anti-PD-1 | [68] |
Notes: VSV, vesicular stomatitis virus; NDV, Newcastle disease virus; HSV, herpes simplex virus; CXCL10, chemokine (C-X-C) motif 10; GM-CSF, granulocyte-macrophagecolony-stimulating factor; MIP-1α, macrophage inflammatory protein-1α; NK, natural killer cells; TAMs, tumor-associated macrophages; TILs, tumor infiltrating lymphocytes.