Cd47 Blockade To Enhance Adaptive Anti-Tumor Immune Responses

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The success of immunotherapy has been hindered by the ability of tumors to evade or inhibit the host immune system. One strategy tumors use to achieve this is upregulation of CD47, a cell surface protein that delivers a “don't eat me” signal. CD47 binds to SIRP-alpha on the surface of macrophages and disables their phagocytic function. Previous data showed CD47 blockade enhanced phagocytosis of tumor cells in vitro and improved survival of mice transplanted with human tumors. However, CD47 blockade has yet to be examined in a fully syngeneic system where the potential for tumor phagocytosis by macrophages and/or dendritic cells to promote presentation of tumor antigens to T cells can be defined. It has been reported that CD47 blockade can hinder T cell activation; however, this also has not been examined in a syngeneic system. Our hypothesis was that inducing tumor cell phagocytosis by CD47 blockade would enhance T-cell-mediated anti-tumor responses. Our data show that CD47 was expressed on the EL4 thymoma and B16-F10 melanoma cell lines that are syngeneic to H-2b, as well as on their ovalbumin-expressing derivatives EG7 and B16-OVA. CD47 also was expressed on CD8+ T cells and was further upregulated upon stimulation, suggesting it might play a role in immune effector function. However, in our hands CD47 blockade using antibody MIAP-301 did not inhibit activation of CD8+ T cells in vitro, and in preliminary experiments, CD47 blockade appeared to enhance activation of antigen-specific CD8+ T cells in vivo. Ongoing work is evaluating the effects of CD47 blockade and phagocytosis on antigen presentation in vitro and the effects of CD47 blockade on the generation of tumor-specific CD4 and CD8 T cells in vivo. We also plan to confirm that T cells activated under conditions of CD47 blockade can recognize endogenous tumor antigens to which there may be self-tolerance. Supported by an HHMI Medical Student Fellowship (to KA), by the GREYlong Foundation, and by grant P01 AI035296 (to MFM). Citation Format: Katie L. Anderson, Daisuke Ito, Debra C. Lins, Julie M. Curtsinger, Matthew F. Mescher, Jaime F. Modiano. CD47 blockade to enhance adaptive anti-tumor immune responses. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4082. doi:10.1158/1538-7445.AM2014-4082