Abstract A82: Evaluation of novel immune target in hematologic malignancies

Abstract

Abstract Background and Objective: Development of drugs such as tyrosine kinase inhibitors (TKIs), immunomodulatory drugs (IMiDs), or proteasome inhibitors (PIs) have improved survival of hematologic malignancies including chronic myeloid leukemia (CML) and multiple myeloma (MM). However, some patients eventually relapse by discontinuation of the drugs or acquiring resistance to the drugs. Thus, it is crucial to develop novel therapy for cure of these malignancies. CML and MM are considered to be relatively immunogenic diseases among hematologic malignancies and immunotherapy might be useful. Since CML cells or MM cells have few somatic mutations which result in amino acid changes and give rise to neoantigens, checkpoint inhibitors alone may not be sufficient to evoke effective immunity against these cells. Instead, overexpressed antigen may be an attractive therapeutic target. We have identified CXorf48 as a highly expressed antigen in several hematologic malignancies including CML and MM. In this study, we investigated whether CXorf48 could serve as a therapeutic target for CML and MM. Methods and Results: High expression of CXorf48 gene in CML cells and MM cells was confirmed by quantitative PCR and also patients’ gene data obtained from a public repository. In contrast, BMMNCs cells or PBMNCs from healthy donor did not express CXorf48. We induced CXorf48-specific cytotoxic T lymphocytes (CTLs) by stimulating lymphocytes from healthy donors with HLA-A24:02-restricted CXorf48-derived epitope peptide. ELISpot assay, cytotoxic assay and CD107a mobilization assay showed that these CTLs preferentially recognized CML cells and MM cells. Moreover, we could detect CXorf48-specific CTL in peripheral blood of CML patients who remained in complete molecular remission after cessation of TKIs. Conclusion: Our data suggest that CXorf48 is a novel therapeutic target of CTLs in CML or MM. Immunotherapy against this antigen, such as vaccination therapy or adoptive T-cell therapy after conventional therapies might be an attractive therapeutic strategy for cure of CML and MM. Citation Format: Maiko Matsushita, Shinya Yokoe, Koji Ozawa, Saori Kanchi, Daiju Ichikawa, Eri Matsuki, Takehiko Mori, Shinichiro Okamoto, Yutaka Hattori. Evaluation of novel immune target in hematologic malignancies [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A82.