Abstract 12380: Preventing Tumor Formation Following iPS Cell-Derived Cardiomyocytes Transplantation Therapy by Carbohydrate Vaccine Therapy Targeting Undifferentiated iPS Cell-Specific Antigen

• Published in: Circulation (New York, N.Y.) N.Y.), 2015-11, Vol.132 (Suppl_3 Suppl 3), p.A12380-A12380
• Main Authors: Kawamura, Takuji, Miyagawa, Shigeru, Fukushima, Satsuki, Kashiyama, Noriyuki, Kawamura, Ai, Yoshida, Shohei, Itou, Emiko, Saito, Atsuhiro, Maeda, Akira, Eguchi, Hiroshi, Toda, Koichi, Miyagawa, Shuji, Okuyama, Hiroomi, Sawa, Yoshiki
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.132.suppl_3.12380

IntroductionCell transplantation therapy using induced pluripotent stem cell (iPSC)-derived cardiomyocyte (iPSC-CM) into damaged myocardium is a promising approach; however, the tumor formation from the remaining undifferentiated iPSCs in the graft is still a concern. We hypothesized that antigens specific to the undifferentiated iPSCs may provoke host immune response after transplantation, and that vaccine therapy targeting the antigen may minimize tumor formation following transplantation of iPSC-CMs.Methods and ResultsMurine iPSCs or iPSC-CMs, were transplanted into syngeneic mice and then the antibodies against each cell in the serum were quantified as mean fluorescence intensity by flow cytometry. As a result, the anti-iPSC antibodies in the iPSC-immunized mice, but not the anti-iPSC-CM antibodies in the iPSC-CM-immunized mice, displayed significantly higher intensities (IgM, 1,400, IgG2,300) as compared to the normal (IgM180, IgG310). Of note, the antibodies against SSEA-1 were significantly increased in the serum of the iPSC-immunized mice (IgM219, IgG216), as compared to the normal (IgM59, IgG56), quantified by the enzyme-linked immunosorbent assay. It was thus indicated that SSEA-1 may be a target to induce undifferentiated iPSC-specific immune response. Then, we immunized mice with SSEA-1 conjugated CRM-197, which is reported to be an effective carrier protein to present carbohydrate antigens. In the serum of the SSEA-1-CRM-197-immunized mice, antibodies against the iPSCs (IgM1,600, IgG2,400) were significantly higher levels than those against the iPSC-CMs (IgM100, IgG200). In addition, CD4+ and CD19+ cells presented significantly higher proliferative responses against the transplanted iPSCs, resulting in depletion of more than 10^7 of the undifferentiated iPSCs in vivo. Finally, transplantation of the iPSC-CMs to the SSEA-1-CRM-197-immunized mice revealed the engraftment of the iPSC-CMs without the tumor formation (n=5).ConclusionsCarbohydrate vaccine targeting SSEA-1 induced the undifferentiated iPSC-specific immune response and enabled the iPSC-CMs to engraft without the tumor formation. This novel approach would be useful to ensure the safety of the iPSC transplantation therapy.