Program: Oral and Poster Abstracts
Session: 203. Lymphocytes, Lymphocyte Activation and Immunodeficiency, including HIV and Other Infections: Poster III
First, we established b3a2-specific CD4+ Th clone from peripheral blood mononuclear cells of a healthy donor positive for HLA-DRB1*09:01 and HLA-A*24:02. The Th clone recognized b3a2 peptide in the context of HLA-DR9 and exhibited a Th1 profile. Second, we established iPSCs from the Th clone and differentiated them into T cell lineage by coculture with OP9 stromal cells expressing Notch ligand Delta-like 1. The iPSC-derived T cells (b3a2-iPS-T cells) expressed the same T cell antigen receptor (TCR) as the original Th clone but not CD4 molecule. Because CD4 acts as a co-receptor in the TCR-mediated Th responses, we transduced b3a2-iPS-T cells with CD4 gene. The CD4-expressing b3a2-iPS-T cells (CD4+ b3a2-iPS-T cells) recognized b3a2 peptide in the context of HLA-DR9 as the original Th clone. Moreover, CD4+ b3a2-iPS-T cells activated by b3a2 peptide induced DC maturation, as indicated by the upregulation of CD86 on DCs. In the additional presence of HLA-A24-restricted Wilms tumor 1 (WT1) peptide, the mature DCs stimulated primary expansion of WT1-specific CTLs. The CTLs exerted cytotoxicity against WT1 peptide-loaded HLA-A24 positive cell lines. These data suggest that the CD4+ b3a2-iPS-T cells have a potential to induce effective anti-leukemic immunity via DC maturation and subsequent CTL responses.
The current approach enable to provide large amounts of b3a2 specific CD4+ Th-like cells that would augment CTL-mediated anti-leukemic responses via DC maturation, which may contribute to the treatment of patients with refractory CML.
Disclosures: Kiyoi: Yakult Honsha Co.,Ltd.: Research Funding ; FUJIFILM Corporation: Patents & Royalties , Research Funding ; Eisai Co., Ltd.: Research Funding ; Kyowa Hakko Kirin Co., Ltd.: Consultancy , Research Funding ; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding ; Zenyaku Kogyo Co., Ltd.: Research Funding ; Novartis Pharma K.K.: Research Funding ; Mochida Pharmaceutical Co., Ltd.: Research Funding ; Astellas Pharma Inc.: Consultancy , Research Funding ; Nippon Shinyaku Co., Ltd.: Research Funding ; FUJIFILM RI Pharma Co.,Ltd.: Research Funding ; Nippon Boehringer Ingelheim Co., Ltd.: Research Funding ; Alexion Pharmaceuticals: Research Funding ; MSD K.K.: Research Funding ; Japan Blood Products Organization: Research Funding ; Takeda Pharmaceutical Co., Ltd.: Research Funding ; Pfizer Inc.: Research Funding ; Bristol-Myers Squibb: Research Funding ; Chugai Pharmaceutical Co., Ltd.: Research Funding ; Taisho Toyama Pharmaceutical Co., Ltd.: Research Funding ; Teijin Ltd.: Research Funding . Naoe: Celgene K.K.: Research Funding ; Otsuka Pharmaceutical Co., Ltd.: Research Funding ; Toyama Chemical CO., LTD.: Research Funding ; Kyowa Hakko Kirin Co., Ltd.: Patents & Royalties , Research Funding ; Chugai Pharmaceutical Co., Ltd.: Patents & Royalties ; FUJIFILM Corporation: Patents & Royalties , Research Funding ; Nippon Boehringer Ingelheim Co., Ltd.: Research Funding ; Pfizer Inc.: Research Funding ; Astellas Pharma Inc.: Research Funding . Kaneko: AsTlym Co., Ltd: Other: founder, shareholder and scientific adviser .
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*signifies non-member of ASH