Abstract 769: Novel cancer immunotherapeutics utilizing targeting peptides

Cancer immunotherapeutics is an emerging treatment option that offers high tumor specificity and efficacy while reducing deleterious side effects. Immune therapies for cancer can be divided into two main types: active and passive. Active therapy strives to achieve a long term protective immunity against a tumor antigen while passive therapy supplies exogenous immunological reagents to provide specific anti-tumor effector functions. Both immunotherapies can be improved through the use of targeting peptides. Our lab utilizes a phage library panning method for isolation of cell-specific peptides that can be rapidly acquired without prior knowledge of cell surface receptors. Active Immunotherapy: Cancer vaccines can elicit an immune response against tumor associated antigens that will result in tumor reduction and protective immunity. Recent studies have utilized antigen-pulsed in vitro matured DCs during vaccination for a more effective anti-cancer immune response. Several clinical trials, however, show that this method does not provide a significant therapeutic immune response. A more robust anti-tumor immune response could potentially be achieved through in vivo targeting of tumor antigens to DCs. Through the phage library panning protocol, our lab has identified 2 phage clones, XS52.1 and XS52.3, which have been shown to specifically bind to the XS52 immature dendritic cells. The XS52.3 phage clone has been further shown to bind bone marrow dendritic cells (BMDCs) from both Balb/c and C57BL/J6 mice. While current data suggests these phage clones are capable of binding DCs in vitro, future studies will determine if these peptides can be used to target antigen to DCs in vivo for vaccination. Passive Immunotherapy: Monoclonal antibodies directed against tumor associated antigens have been successfully used in clinical settings, but problems remain with identifying and validating new antigen targets. Modification of the antibody scaffold for distinct applications can also be problematic. Using our phage display panning protocol, we have identified ligands of high affinity and specificity against a panel of human non-small cell lung cancer (NSCLC) cell lines. Furthermore, these peptide targeting ligands can be chemically synthesized and easily modified for different uses. For example, synthetic peptide ligands have been used to direct antibody dependant cellular cytotoxicity through the use of biotinylated tetrameric peptides and anti-biotin antibodies. These results suggest that peptide targeting ligands can be used to direct antibody effector functions for passive immunotherapy against cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 769. doi:10.1158/1538-7445.AM2011-769