Mark O Hardin1, Timothy J Vreeland2, Guy T Clifton2, Diane F Hale3, Garth S Herbert3, Julia M Greene3, Doreen O Jackson3, John E Berry3, Pauline Nichols4, Sook Yin5, Xianzhong Yu6, Thomas E Wagner4, George E Peoples4,7,8. 1. Department of Surgery, Madigan Army Medical Center, Ft. Lewis, WA 98431, USA. 2. Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 3. Department of Surgery, San Antonio Military Medical Center, Ft. Sam Houston, TX 78234, USA. 4. Orbis Health Solutions, Greenville, SC 29607, USA. 5. Perseus PCI, George Town, Grand Cayman, Cayman Islands. 6. Department of Biological Sciences, Clemson University, Clemson, SC 29631, USA. 7. Cancer Vaccine Development Program, San Antonio, TX 78234, USA. 8. Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Abstract
AIM: We developed a novel approach to efficiently deliver autologous tumor antigens to the cytoplasm of dendritic cells (DC) using yeast cell wall particles (YCWP). MATERIALS AND METHODS: Loading of YCWP, leakage of protein from loaded YCWP and cytoplasmic delivery of YCWP content was assessed using fluorescent-tagged experiments. Spectrophotometric analysis compared the epitope-specific T-cell responses following antigen presentation via YCWP versus exogenous loading. The in vivo effectiveness of tumor lysate (TL) particle loaded DC (TLPLDC) vaccine was assessed using murine melanoma models. RESULTS: In fluorescence-tagged experiments, YCWP efficiently delivered antigen to the cytoplasm of DC. TLPLDC loading was more effective than conventional exogenous loading of DC. Finally, in murine melanoma models, TLPLDC outperformed an analogous dendritoma vaccine. CONCLUSION: The TLPLDC vaccine is commercially scalable and holds the potential of producing personalized vaccines.
AIM: We developed a novel approach to efficiently deliver autologous tumor antigens to the cytoplasm of dendritic cells (DC) using yeast cell wall particles (YCWP). MATERIALS AND METHODS: Loading of YCWP, leakage of protein from loaded YCWP and cytoplasmic delivery of YCWP content was assessed using fluorescent-tagged experiments. Spectrophotometric analysis compared the epitope-specific T-cell responses following antigen presentation via YCWP versus exogenous loading. The in vivo effectiveness of tumor lysate (TL) particle loaded DC (TLPLDC) vaccine was assessed using murinemelanoma models. RESULTS: In fluorescence-tagged experiments, YCWP efficiently delivered antigen to the cytoplasm of DC. TLPLDC loading was more effective than conventional exogenous loading of DC. Finally, in murinemelanoma models, TLPLDC outperformed an analogous dendritoma vaccine. CONCLUSION: The TLPLDC vaccine is commercially scalable and holds the potential of producing personalized vaccines.