Table 1.
Virotherapy studies employing tumor cell spheroids
| 3-D culture system | Tumor entity | OV | Notes | Reference |
|---|---|---|---|---|
| Spheroids | Bladder cancer | Adenovirus | Targeting cancer-initiating cells with an OV | 19 |
| Colon carcinoma | Adenovirus | Mechanism of viral spread and penetration in epithelial tissue | 25 | |
| Echovirus | Oncolytic activity in 2-D and 3-D cultures | 26 | ||
| Echovirus 5 | Using an altered infectious nucleic acid to initiate and improve viral replication | 27 | ||
| Newcastle disease virus | Development of more potent OVs by bioselection | 28 | ||
| Glioblastoma | HSV1 | Replication and oncolytic activity in animal models and spheroids | 29 | |
| Reovirus | Analysis of oncolytic activity in 2-D and 3-D glioblastoma stem-like cells | 21 | ||
| Reovirus | Different entry pathways in 2-D and spheroid cultures | 17 | ||
| VSV | Development and testing of a semireplication-competent VSV to improve safety | 30 | ||
| Glioblastoma, neuroblastoma | HSV1 | Degradation of ECM to enhance oncolytic activity | 31 | |
| Glioma | Adenovirus | Analysis of oncolytic activity, combinatorial virotherapy with temozolomide and suicide gene | 6 | |
| Adenovirus | Evaluation of oncolytic activity with PET and WST1 assay | 24 | ||
| Adenovirus | Combination of radiation and OV | 14 | ||
| Glioma, breast cancer | Adenovirus | Decorin transgene to improve viral spread by degrading the ECM | 32 | |
| Hepatocellular carcinoma | Adenovirus | Targeting Wnt signaling in hepatocellular carcinoma stem-like cells | 20 | |
| Lung cancer | Adenovirus | Targeting lung cancer stem-like cells | 18 | |
| Melanoma, breast cancer | HSV2 | Oncolytic mechanism and role of the calpain system in cancer stem-like cells | 33 | |
| NSCLC | Newcastle disease virus | Oncolytic mechanism of Newcastle disease virus, influence of autophagy | 34 | |
| Ovarian cancer | Adenovirus | Measurement of oncolysis in spheroids via luciferase expression | 13 | |
| Adenovirus | Different efficacy in different patient samples | 35 | ||
| Adenovirus | Virus replication and measurement in 3-D cultures | 12 | ||
| Adenovirus | Development and preclinical testing of a novel OV | 36 | ||
| Echovirus 1 | Preclinical testing of oncolytic potential | 37 | ||
| Myxoma virus | Different oncolytic activity in adherent and nonadherent cells | 15 | ||
| Myxoma virus, vaccinia virus, Maraba virus | Different oncolytic activity in 2D vs 3-D cultures | 16 | ||
| Vaccinia virus | Targeting cancer-initiating cells with chemokine-receptor antagonist expressing OV | 38 | ||
| Pancreatic cancer | Adenovirus | Reduction of gemcitabine resistance by degrading ECM with OV | 39 | |
| Panel of tumor cell lines | Adenovirus | Degradation of ECM to increase viral distribution and penetration | 40 | |
| Panel of tumor cell lines | Coronavirus | Targeting coronaviruses to EGF receptor with a bispecific antibody | 41 | |
| Pediatric glioma | HSV1 | Oncolytic mechanism of action, OV as an anti-invasive treatment | 42 | |
| Spheroids, chicken chorioallantoic membrane models | Pancreatic cancer | Adenovirus | OV delivery using mesenchymal stromal cells | 43 |
| Spheroids placed on brain slices | Glioma | HSV1 | ECM degradation by chondroitinase ABC enhances antitumor efficacy | 10 |
| Vaccinia virus | Influence of microglia and astrocytes on oncolytic activity | 44 | ||
| Spheroid coculture in PEG diacrylate hydrogels | Glioblastoma | Adenovirus | Oncolytic potential in 3-D cocultures | 9 |
| Neurospheres | Glioblastoma | Adenovirus | Targeting brain-tumor stem-like cells | 45 |
| Adenovirus | Targeting brain-tumor stem-like cells, role of autophagy | 8 | ||
| HSV1 | Sensitizing of glioblastomas to temozolomide by OV expressing chondroitinase M | 46 | ||
| Measles vaccine virus | Preclinical testing of OV in tumor stem-like cells | 22 | ||
| Parvovirus H1 | Oncolytic activity in glioblastoma stem-like cells | 23 |
Abbreviations: 2-D, two-dimensional; 3-D, three-dimensional; ECM, extracellular matrix; HSV, herpes simplex virus; NSCLC, non-small-cell lung cancer; OV, oncolytic virus; PEG, polyethylene glycol; PET, positron-emission tomography; VSV, vesicular stomatitis virus.