Abstract 5596: Intratumoral administration of a TLR9-adjuvanted nanoparticle cancer vaccine stimulates more effective immunity in both injected and un-injected tumor sites compared to subcutaneous administration

Abstract

Abstract Therapeutic success of a cancer vaccine requires substantial expansion of vaccine-primed CTL and efficient differentiation to polyfunctional T cells capable of migrating from the site of vaccination to metastatic sites. We have evaluated the tumor itself as a potential site of vaccination, compared to vaccination at subcutaneous sites distant from the tumor. For vaccination, we have developed a highly efficient nanoparticle platform comprised of multiple copies of a CpG-rich oligonucleotide (a TLR9 agonist) and long peptide tumor antigens, both covalently linked to the sucrose polymer Ficoll. Multiple peptide antigens where studied, including ovalbumin and a long peptide comprising epitopes from three melanocyte differentiation antigens. In all of these models, intratumoral vaccination was superior to subcutaneous vaccination for elimination of both injected tumors and, more importantly, distant site skin and lung metastases. Intratumoral vaccination substantially increased the magnitude of the systemic CTL response measured in the blood and in the spleen and enhanced capacity cell homing to distant site tumors. A greater fraction of tumor-antigen specific CD8+ T cells generated in the tumor were polyfunctional, expressing both IFN-γ and TNF-α. They were also less exhausted as measured by decreased overall PD-1 levels, increased T bet and the increased number of PD-1+ cells that retained cytotoxicity and proliferative capacity. Intratumoral vaccination also induced spread of the CD8+ T cell response to tumor antigens not included in the vaccine. These results demonstrate that direct intratumoral immunization with peptide antigens combined with a strong TLR9-activating adjuvant significantly increases the magnitude and quality of vaccine-primed CTL and enhances control of metastatic disease. Note: This abstract was not presented at the meeting. Citation Format: Edwina Naik, Chi Ying, Robert Milley, Carlo Calacsan, Stewart Chipman, Thomas Tüting, Robert Coffman, Cristiana Guiducci. Intratumoral administration of a TLR9-adjuvanted nanoparticle cancer vaccine stimulates more effective immunity in both injected and un-injected tumor sites compared to subcutaneous administration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5596. doi:10.1158/1538-7445.AM2017-5596