Cyto-Immuno-Therapy for Cancer: A Pathway Elicited by Tumor-Targeted, Cytotoxic Drug-Packaged Bacterially Derived Nanocells

• Published in: Cancer cell Vol. 37; no. 3; pp. 354 - 370.e7
• Main Authors: Sagnella, Sharon M., Yang, Lu, Stubbs, Gemma E., Boslem, Ebru, Martino-Echarri, Estefania, Smolarczyk, Katarzyna, Pattison, Stacey L., Vanegas, Natasha, St. Clair, Eva, Clarke, Stephen, Boockvar, John, MacDiarmid, Jennifer A., Brahmbhatt, Himanshu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.03.2020
• Subjects: cancer; combined therapeutic; cyto-immunotherapy; immunotherapy; nanocell; PNU-159682; supercytotoxin; tumor targeting; tumor targeting; supercytotoxin; immunotherapy; cyto-immunotherapy; cancer; nanocell; combined therapeutic; PNU-159682
• ISSN: 1535-6108; 1878-3686
• DOI: 10.1016/j.ccell.2020.02.001

Immunotherapy has emerged as a powerful new chapter in the fight against cancer. However, it has yet to reach its full potential due in part to the complexity of the cancer immune response. We demonstrate that tumor-targeting EDV nanocells function as an immunotherapeutic by delivering a cytotoxin in conjunction with activation of the immune system. These nanocells polarize M1 macrophages and activate NK cells concurrently producing a Th1 cytokine response resulting in potent antitumor function. Dendritic cell maturation and antigen presentation follows, which generates tumor-specific CD8+ T cells, conferring prolonged tumor remission. The combination of cytotoxin delivery and activation of innate and adaptive antitumor immune responses results in a potent cyto-immunotherapeutic with potential in clinical oncology. [Display omitted] •EnGeneIC Dream Vector (EDV) nanocells induce an antitumor innate immune cell response•EDV treatment results in tumor-specific T cells and an adaptive immune response•EDV treatment elicits a predominantly Th1 response•Dual assault on EDV-treated tumors confers long-term survival Sagnella et al. report the immune modulatory effects of EnGeneIC Dream Vectors (EDVs), bacterially derived nonviable nanocells bearing cytotoxic payloads, in mouse models and human cancer patients. In addition to cytotoxicity, EDVs induce innate and adaptive immune responses to elicit antitumor effects.