Multifaceted cancer alleviation by cowpea mosaic virus in a bioprinted ovarian cancer peritoneal spheroid model

Yi Xiang; Zhongchao Zhao; Emmie J Yao; Alis Balayan; Steven N Fiering; Nicole F Steinmetz; Shaochen Chen

doi:10.1016/j.biomaterials.2024.122663

Multifaceted cancer alleviation by cowpea mosaic virus in a bioprinted ovarian cancer peritoneal spheroid model

Biomaterials. 2024 Dec:311:122663. doi: 10.1016/j.biomaterials.2024.122663. Epub 2024 Jun 10.

Authors

Yi Xiang¹, Zhongchao Zhao², Emmie J Yao¹, Alis Balayan³, Steven N Fiering⁴, Nicole F Steinmetz⁵, Shaochen Chen⁶

Affiliations

¹ Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
² Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; Center for Nano-ImmunoEngineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; Moores Cancer Center, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
³ Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; School of Medicine, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA.
⁴ Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, 03756, USA; Dartmouth Cancer Center, Geisel School of Medicine at Dartmouth and Dartmouth Health, Lebanon, NH, 03756, USA.
⁵ Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; Center for Nano-ImmunoEngineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; Moores Cancer Center, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; Department of Radiology, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; Shu Chien-Gene Lay Department of Bioengineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; Institute for Materials Discovery and Design, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; Center for Engineering in Cancer, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; Shu and K.C. Chien and Peter Farrell Collaboratory, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA. Electronic address: nsteinmetz@ucsd.edu.
⁶ Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; Center for Nano-ImmunoEngineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; Shu Chien-Gene Lay Department of Bioengineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA; Institute for Materials Discovery and Design, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA, 92093, USA. Electronic address: shc064@ucsd.edu.

Abstract

Ovarian cancer (OvCa) is a leading cause of mortality among gynecological malignancies and usually manifests as intraperitoneal spheroids that generate metastases, ascites, and an immunosuppressive tumor microenvironment. In this study, we explore the immunomodulatory properties of cowpea mosaic virus (CPMV) as an adjuvant immunotherapeutic agent using an in vitro model of OvCa peritoneal spheroids. Previous findings highlighted the potent efficacy of intratumoral CPMV against OvCa in mouse tumor models. Leveraging the precision control over material deposition and cell patterning afforded by digital-light-processing (DLP) based bioprinting, we constructed OvCa-macrophage spheroids to mimic peritoneal spheroids using gelatin methacrylate (GelMA), a collagen-derived photopolymerizable biomaterial to mimic the extracellular matrix. Following CPMV treatment, bioprinted spheroids exhibited inhibited OvCa progression mediated by macrophage activation. Our analysis indicates that CPMV regulates and activates macrophage to both induce OvCa cell killing and restore normal cell-cell junctions. This study deepened our understanding of the mechanism of CPMV intratumoral immunotherapy in the setting of OvCa. This study also highlights the potential of studying immunotherapies using high throughput tissue models via DLP bioprinting.

Keywords: 3D bioprinting; Cancer immunotherapy; Cowpea mosaic virus; In vitro models; Ovarian cancer.

MeSH terms

Animals
Bioprinting* / methods
Cell Line, Tumor
Comovirus*
Female
Humans
Immunotherapy / methods
Macrophages / virology
Mice
Ovarian Neoplasms* / pathology
Ovarian Neoplasms* / virology
Spheroids, Cellular* / pathology
Spheroids, Cellular* / virology

Abstract

MeSH terms

Grants and funding