PMID- 36361783 OWN - NLM STAT- MEDLINE DCOM- 20221114 LR - 20221117 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 21 DP - 2022 Oct 27 TI - Capability of Human Dendritic Cells Pulsed with Autologous Induced Pluripotent Stem Cell Lysate to Induce Cytotoxic T Lymphocytes against HLA-A33-Matched Cancer Cells. LID - 10.3390/ijms232112992 [doi] LID - 12992 AB - Irradiated murine induced-pluripotent stem cells (iPSCs) elicit the antitumor response in vivo. However, it is unclear whether human iPSCs would elicit antitumor effects. In the present study, we investigated the capability of human iPSC lysate (iPSL)-pulsed dendritic cells (DCs) (iPSL/DCs) to induce cancer-responsive cytotoxic T lymphocytes (CTLs) in vitro. iPSCs and DCs were induced from peripheral blood mononuclear cells isolated from a human leukocyte antigen (HLA)-A33 homozygous donor. The iPSL was pulsed with immature DCs, which were then stimulated to allow full maturation. The activated DCs were co-cultured with autologous CTLs and their responses to SW48 colorectal carcinoma cells (HLA-A32/A33), T47D breast cancer cells (HLA-A33/A33), and T98G glioblastoma cells (HLA-A02/A02) were tested with enzyme-linked immunospot (ELISPOT) assays. Comprehensive gene expression analysis revealed that the established iPSCs shared numerous tumor-associated antigens with the SW48 and T47D cells. Immunofluorescent analysis demonstrated that the fluorescent-labeled iPSL was captured by the immature DCs within 2 h. iPSL/DCs induced sufficient CTL numbers in 3 weeks for ELISPOT assays, which revealed that the induced CTLs responded to SW48 and T47D cells. Human iPSL/DCs induced cancer-responsive CTLs on HLA-A33-matched cancer cells in vitro and could be a promising universal cancer vaccine for treating and preventing cancer. FAU - Nakazawa, Tsutomu AU - Nakazawa T AUID- ORCID: 0000-0003-4286-9356 AD - Department of Research and Development, Grandsoul Research Institute for Immunology, Matsui 8-1, Utano, Uda 633-2221, Nara, Japan. AD - Clinic Grandsoul Nara, Matsui 8-1, Utano, Uda 633-2221, Nara, Japan. AD - Department of Neurosurgery, Nara Medical University, Kashihara 634-8522, Nara, Japan. FAU - Maeoka, Ryosuke AU - Maeoka R AUID- ORCID: 0000-0003-1441-838X AD - Department of Neurosurgery, Nara Medical University, Kashihara 634-8522, Nara, Japan. FAU - Morimoto, Takayuki AU - Morimoto T AUID- ORCID: 0000-0002-9974-3538 AD - Department of Neurosurgery, Nara Medical University, Kashihara 634-8522, Nara, Japan. FAU - Matsuda, Ryosuke AU - Matsuda R AUID- ORCID: 0000-0002-0307-3657 AD - Department of Neurosurgery, Nara Medical University, Kashihara 634-8522, Nara, Japan. FAU - Nakamura, Mitsutoshi AU - Nakamura M AUID- ORCID: 0000-0002-7920-2048 AD - Clinic Grandsoul Nara, Matsui 8-1, Utano, Uda 633-2221, Nara, Japan. AD - Department of Neurosurgery, Nara Medical University, Kashihara 634-8522, Nara, Japan. FAU - Nishimura, Fumihiko AU - Nishimura F AD - Department of Neurosurgery, Nara Medical University, Kashihara 634-8522, Nara, Japan. FAU - Yamada, Shuichi AU - Yamada S AUID- ORCID: 0000-0002-7278-3978 AD - Department of Neurosurgery, Nara Medical University, Kashihara 634-8522, Nara, Japan. FAU - Nakagawa, Ichiro AU - Nakagawa I AUID- ORCID: 0000-0002-1340-3293 AD - Department of Neurosurgery, Nara Medical University, Kashihara 634-8522, Nara, Japan. FAU - Park, Young-Soo AU - Park YS AD - Department of Neurosurgery, Nara Medical University, Kashihara 634-8522, Nara, Japan. FAU - Nakase, Hiroyuki AU - Nakase H AUID- ORCID: 0000-0002-2726-5960 AD - Department of Neurosurgery, Nara Medical University, Kashihara 634-8522, Nara, Japan. FAU - Tsujimura, Takahiro AU - Tsujimura T AD - Department of Research and Development, Grandsoul Research Institute for Immunology, Matsui 8-1, Utano, Uda 633-2221, Nara, Japan. AD - Clinic Grandsoul Nara, Matsui 8-1, Utano, Uda 633-2221, Nara, Japan. LA - eng PT - Journal Article DEP - 20221027 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (HLA-A*33 antigen) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (HLA Antigens) SB - IM MH - Humans MH - Mice MH - Animals MH - T-Lymphocytes, Cytotoxic MH - *Induced Pluripotent Stem Cells MH - Leukocytes, Mononuclear/metabolism MH - Dendritic Cells MH - Histocompatibility Antigens Class II/metabolism MH - HLA Antigens/metabolism MH - *Neoplasms/metabolism PMC - PMC9654950 OTO - NOTNLM OT - cancer immunotherapy OT - cancer vaccine OT - cytotoxic lymphocyte (CTL) OT - dendritic cell (DC) OT - induced pluripotent stem cell (iPSC) COIS- T.N. and M.N. are registered as research fellows at Nara Medical University. EDAT- 2022/11/12 06:00 MHDA- 2022/11/15 06:00 PMCR- 2022/10/27 CRDT- 2022/11/11 01:25 PHST- 2022/10/02 00:00 [received] PHST- 2022/10/25 00:00 [revised] PHST- 2022/10/25 00:00 [accepted] PHST- 2022/11/11 01:25 [entrez] PHST- 2022/11/12 06:00 [pubmed] PHST- 2022/11/15 06:00 [medline] PHST- 2022/10/27 00:00 [pmc-release] AID - ijms232112992 [pii] AID - ijms-23-12992 [pii] AID - 10.3390/ijms232112992 [doi] PST - epublish SO - Int J Mol Sci. 2022 Oct 27;23(21):12992. doi: 10.3390/ijms232112992.