Abstract 1814: Harnessing the potential of idiotypic peptide therapy for the treatment of multiple myeloma

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Abstract BACKGROUND: The idiotype determinant of surface Immunoglobulin B-Cell Receptor (IgBCR) is the most reliable clonal marker of tumor cell population and can be exploited for novel targeting approaches. We previously developed a novel experimental approach to identify peptide ligands of the IgBCR idiotype determinant of neoplastic B cells, named “Id-peptides” (Palmieri C., Blood 2010). These Id-peptides were validated as a tool for specific targeting of B-cell malignancies with a potential role as modulators of tumor microenvironment via sIgBCR signalling. In Multiple Myeloma (MM), both mature and clonogenic tumor stem cells (clonotype B-lymphocytes, CBLs) share the same antigenic specificity, making these cells a suitable target for Id-peptides. In this regard, we have recently developed Id-peptides for tumor targeting in primary neoplastic plasma cells as well as in the 5T33MM mouse model of MM. RESULTS: Tumor-specific Id-peptides of MM (n=8), or MGUS (n=2) patients were selected by screening phage-displayed random peptide libraries using the cognate serum IgG paraprotein as bait. The selected Id-peptides specifically bound to the cognate primary neoplastic plasma cells, as shown by FACS analysis. By confocal microscopy, we observed that each patient-specific Id-peptide co-localized with the sIgG-BCR at the cell surface of the cognate neoplastic plasma cell. Further, the Id-peptides were able to target CD138pos differentiated plasma cells as well as a number of less differentiated CD138neg, IgGpos and CD19pos bone marrow B-cells, suggesting that they tracked the clonogenic precursors of MM cells. Using the same screening approach in the 5T33MM mouse model of MM, Id-peptides were able to specifically detect a significant proportion of target cancer cells in the peripheral blood of diseased animal. Interestingly, the in vivo exposure of 5T33 murine MM cells to Id-peptides resulted in a reduced expression of immunosuppressive cytokines genes (Tgfb1 and Il10) and pro-angiogenic genes (Vegf, Tbxas, SDF, Il8, CXCr4). CONCLUSION: This study demonstrates that Id-peptides can be used to identify and purify the clonotypic precursors of MM cells, thus providing a unique tool for assessing both the phenotypic and functional features of the still poorly characterized MM “cancer stem cell” compartment. Moreover, the Id-peptides can inhibit the expression of genes that are crucial to promote a functional MM microenvironment and angiogenesis, thus representing a potential tool for MM therapy. Note: This abstract was not presented at the meeting. Citation Format: Enrico Iaccino, Selena Mimmi, Cristina Falcone, Eleonora Vecchio, Roberta Crescenzo, Giuseppina Maggisano, Cesare Carvelli, Samuela Russo, Annamaria de Laurentiis, Marilena Pontoriero, Antonio Pisano, Simona Ceglia, Francesca Fasanella Masci, Annarita Scialdone, Annalisa Rossi, Giuseppe Fiume, Camillo Palmieri, Ileana Quinto, Giuseppe Scala. Harnessing the potential of idiotypic peptide therapy for the treatment of multiple myeloma. [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 1814. doi:10.1158/1538-7445.AM2014-1814