Tumor RNA transfected DCs derived from iPS cells elicit cytotoxicity against cancer cells induced from colorectal cancer patients in vitro

Significant efficacy of induced pluripotent stem cells (iPSCs) in generating DCs for cancer vaccine therapy was suggested in our previous studies. In clinical application of DC vaccine therapy, however, few DC vaccine systems have shown strong clinical response. To enhance immunogenicity in the DC v...

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Veröffentlicht in:Scientific reports 2022-02, Vol.12 (1), p.3295-3295, Article 3295
Hauptverfasser: Maruoka, Shimpei, Ojima, Toshiyasu, Iwamoto, Hiromitsu, Kitadani, Junya, Tabata, Hirotaka, Tominaga, Shinta, Katsuda, Masahiro, Hayata, Keiji, Takeuchi, Akihiro, Yamaue, Hiroki
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Sprache:eng
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Zusammenfassung:Significant efficacy of induced pluripotent stem cells (iPSCs) in generating DCs for cancer vaccine therapy was suggested in our previous studies. In clinical application of DC vaccine therapy, however, few DC vaccine systems have shown strong clinical response. To enhance immunogenicity in the DC vaccine, we transfected patient-derived iPSDCs with in vitro transcriptional RNA (ivtRNA), which was obtained from tumors of three patients with colorectal cancer. We investigated iPSDCs-ivtRNA which were induced by transfecting ivtRNA obtained from tumors of three colorectal cancer patients, and examined its antitumor effect. Moreover, we analyzed neoantigens expressed in colorectal cancer cells and examined whether iPSDCs-ivtRNA induced cytotoxic T lymphocytes (CTLs) against the predicted neoantigens. CTLs activated by iPSDCs-ivtRNA exhibited cytotoxic activity against the tumor spheroids in all three patients with colorectal cancer. Whole-exome sequencing revealed 1251 nonsynonymous mutations and 2155 neoantigens (IC 50  
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-07305-1