Zhongchao Zhao

A co-formulated vaccine of irradiated cancer cells and cowpea mosaic virus improves ovarian cancer rejection

Cowpea mosaic virus adjuvants bind to irradiated cancer cells (ICCs) – the co-delivery of ICCs (the antigen) and CPMV (the adjuvant) demonstrates potent efficacy as a vaccine that protects mice from ovarian tumor challenge.

Cisplatin-Loaded Tobacco Mosaic Virus for Ovarian Cancer Treatment

Ovarian cancer is the foremost cause of gynecological cancer and a major cause of cancer death in women. Treatment for advanced stage is surgical debulking followed by chemotherapy; however, most patients relapse with more aggressive and therapy-resistant tumors. There is a need to develop drug delivery approaches to deliver platinum therapies to tumors to increase efficacy while maintaining safety. Toward this goal, we utilized the protein nanotubes from the plant virus, tobacco mosaic virus (TMV), as a drug carrier. Specifically, the nanochannel of TMV was loaded with the active dication form of cisplatin (cisPt

A cowpea mosaic virus adjuvant conjugated to liposomes loaded with tumor cell lysates as an ovarian cancer vaccine

Abstract Current treatment options for ovarian cancer are limited to surgery to remove tumor tissues and chemotherapy. Although such treatments could provide a short period of remission, most patients still experience recurrent metastatic diseases. Here we present a nanotechnology-based personalized cancer vaccine that can be administrated to patients during the remission stage to prevent recurrent diseases. Autologous tumor cell lysates (TCL) are intriguing, personalized antigens that could be extracted from surgically recovered tumor tissues from patients containing all neoantigens. As proof of concept, we use TCL isolated from a murine ovarian cancer cell line. TCL are first encapsulated in liposomes (TCL-Lip), which are then attached to cowpea mosaic virus (CPMV), a plant virus as a potent adjuvant. Using the ID8-Defb29/Vegf-a-Luc tumor model in female mice, the TCL-Lip-CPMV conjugate vaccine protects mice from tumor challenge by improving antigen processing and presentation, priming an adaptive anti-tumor immunity. Using ovalbumin (OVA) as a model antigen, OVA-Lip-CPMV vaccination protects mice from lung metastasis post-surgical removal of the primary B16F10-OVA dermal tumors. This research establishes a platform by combining two nanoparticle technologies into a single formulation for the simultaneous delivery of antigens and adjuvants, advancing the development of cancer vaccines and immunotherapies.

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

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.