American Association for Cancer Research

sorry, we can't preview this file

23266066cir210193-sup-261987_2_supp_7313091_qxl5hb.docx (413.69 kB)

Supplementary Figure and Table from iPSC-Derived Neoantigen-Specific CTL Therapy for Ewing Sarcoma

Download (413.69 kB)
journal contribution
posted on 2023-04-04, 01:07 authored by Midori Ishii, Jun Ando, Satoshi Yamazaki, Tokuko Toyota, Kazuo Ohara, Yoshiki Furukawa, Yoshiyuki Suehara, Mahito Nakanishi, Kazutaka Nakashima, Koichi Ohshima, Hiromitsu Nakauchi, Miki Ando

Supplementary Figure 1 with legend and Supplementary Table 1




The Promotion and Mutual Aid Corporation for Private Schools of Japan



The prognosis of Ewing sarcoma caused by EWS/FLI1 fusion is poor, especially after metastasis. Although therapy with CTLs targeted against altered EWS/FLI1 sequences at the gene break/fusion site may be effective, CTLs generated from peripheral blood are often exhausted because of continuous exposure to tumor antigens. We addressed this by generating induced pluripotent stem cell (iPSC)–derived functionally rejuvenated CTLs (rejT) directed against the neoantigen encoded by the EWS/FLI1 fusion gene. In this study, we examined the antitumor effects of EWS/FLI1-rejTs against Ewing sarcoma. The altered amino acid sequence at the break/fusion point of EWS/FLI1, when presented as a neoantigen, evokes an immune response that targets EWS/FLI1+ sarcoma. Although the frequency of generated EWS/FLI1-specific CTLs was only 0.003%, we successfully established CTL clones from a healthy donor. We established iPSCs from a EWS/FLI1-specific CTL clone and redifferentiated them into EWS/FLI1-specific rejTs. To evaluate cytotoxicity, we cocultured EWS/FLI1-rejTs with Ewing sarcoma cell lines. EWS/FLI1-rejTs rapidly and continuously suppressed the proliferation of Ewing sarcoma for >40 hours. Using a Ewing sarcoma xenograft mouse model, we verified the antitumor effect of EWS/FLI1-rejTs via imaging, and EWS/FLI1-rejTs conferred a statistically significant survival advantage. “Off-the-shelf” therapy is less destructive and disruptive than chemotherapy, and radiation is always desirable, particularly in adolescents, whom Ewing sarcoma most often affects. Thus, EWS/FLI1-rejTs targeting a Ewing sarcoma neoantigen could be a promising new therapeutic tool.

Usage metrics

    Cancer Immunology Research



    Ref. manager