Abstract 12380: Preventing Tumor Formation Following iPS Cell-Derived Cardiomyocytes Transplantation Therapy by Carbohydrate Vaccine Therapy Targeting Undifferentiated iPS Cell-Specific Antigen
Introduction: Cell 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 Results: Murine 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, IgG: 2,300) as compared to the normal (IgM: 180, IgG: 310). Of note, the antibodies against SSEA-1 were significantly increased in the serum of the iPSC-immunized mice (IgM: 219, IgG: 216), as compared to the normal (IgM: 59, IgG: 56), 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 (IgM: 1,600, IgG: 2,400) were significantly higher levels than those against the iPSC-CMs (IgM: 100, IgG: 200). 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).
Conclusions: Carbohydrate 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.
Author Disclosures: T. Kawamura: None. S. Miyagawa: None. S. Fukushima: None. N. Kashiyama: None. A. Kawamura: None. S. Yoshida: None. E. Itou: None. A. Saito: None. A. Maeda: None. H. Eguchi: None. K. Toda: None. S. Miyagawa: None. H. Okuyama: None. Y. Sawa: None.
- © 2015 by American Heart Association, Inc.