Tumor Membrane Vesicle Vaccine Augments the Efficacy of Anti-PD1 Antibody in Immune Checkpoint Inhibitor-Resistant Squamous Cell Carcinoma Models of Head and Neck Cancer

• Type of Material: Article
• Authors: Ramireddy Bommireddy, Emory University; Luis E. Munoz, Emory University; Anita Kumari, Emory University; Lei Huang, Emory University; Yijian Fan, Emory University; Lenore Monterroza, Emory University; Christopher D. Pack, Metaclipse Therapeutics Corporation; Sampath Ramachandiran, Metaclipse Therapeutics Corporation; Shaker J. C. Reddy, Metaclipse Therapeutics Corporation; Janet Kim, Emory University; Georgia Chen, Emory University; Nabil Saba, Emory University; Dong Shin, Emory University; Periasamy Selvaraj, Emory University
• Language: English
• Date: 2020-06-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/vaccines8020182
• Title of Journal or Parent Work: Vaccines
• Volume: 8
• Issue: 2
• Grant/Funding Information: NCI/NIH SBIR Phase I and Phase II grants (CA 176920 and CA 221559 to C.P.); NCI/NIH R01 grant (R01 CA202763 to P.S. and C.P.); This work was supported by Head and Neck SPORE pilot funding from the Winship Cancer Institute (to D.M.S. and N.F.S.); And a seed grant from the Georgia Research Alliance based in Atlanta, Georgia.; Diversity Supplement (R01 CA202763-S to L.E.M.)
• Keywords: B7-1; Nivolumab; cancer; PD-L1; SCCVII; vaccine; HNSCC; Mouse; Immunology; Life Sciences & Biomedicine; IL-12; Research & Experimental Medicine; MOC2; Protein transfer; adjuvants; MOC1; Immunotherapy; Science & Technology; anti-PD1; Recurrent; Medicine, Research & Experimental; Investigators choice; Checkmate 141; TMVs; Anchored cytokines
• Research Categories: Health Sciences, Oncology; Biology, Cell; Health Sciences, Immunology; Health Sciences, Rehabilitation and Therapy

Abstract

Immune checkpoint inhibitor (ICI) immunotherapy improved the survival of head and neck squamous cell carcinoma (HNSCC) patients. However, more than 80% of the patients are still resistant to this therapy. To test whether the efficacy of ICI therapy can be improved by vaccine-induced immunity, we investigated the efficacy of a tumor membrane-based vaccine immunotherapy in murine models of HNSCC. The tumors, grown subcutaneously, are used to prepare tumor membrane vesicles (TMVs). TMVs are then incorporated with glycolipid-anchored immunostimulatory molecules GPI-B7-1 and GPI-IL-12 by protein transfer to generate the TMV vaccine. This TMV vaccine inhibited tumor growth and improved the survival of mice challenged with SCCVII tumor cells. The tumor-free mice survived for several months, remained tumor-free, and were protected following a secondary tumor cell challenge, suggesting that the TMV vaccine induced an anti-tumor immune memory response. However, no synergy with anti-PD1 mAb was observed in this model. In contrast, the TMV vaccine was effective in inhibiting MOC1 and MOC2 murine oral cancer models and synergized with anti-PD1 mAb in extending the survival of tumor-bearing mice. These observations suggest that tumor tissue based TMV vaccines can be harnessed to develop an effective personalized immunotherapy for HNSCC that can enhance the efficacy of immune checkpoint inhibitors.