著者

Shinichiro Motohashi

出版者

International Society of Personalized Medicne

雑誌

Personalized Medicine Universe (ISSN:21864969)

巻号頁・発行日

vol.11, pp.14-19, 2022-11-01 (Released:2022-11-01)

参考文献数

40

被引用文献数

1

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Purpose: This review aims to introduce the previous autologous invariant natural killer T (iNKT) cell-targeted cancer immunotherapy and an ongoing clinical trial using allogeneic induced pluripotent stem cell-derived NKT cells (iPS-NKT cells) for head and neck cancer (HNC).Study selection: Combination therapies of adoptive immunotherapy using ex vivo activated iNKT cells derived from cancer-bearing patients and active immunotherapy using ligand-pulsed antigen presenting cells (APCs) are summarized. Since the preparation of functionally sufficient iNKT cells taken from advanced cancer patients was difficult, a robust protocol to generate iNKT cells in vitro via iPS cells was established. Investigator-initiated clinical trials of iPS-NKT cells were also conducted.Results: The combination therapy with α-GalCer-pulsed APCs and adoptive transfer of autologous iNKT cells showed an objective clinical response. An establishment of in vitro generation of iNKT cells from iPS cells allowed us to ensure sufficient expansion of iNKT cells. Based on the preclinical examinations, a phase I study of allogenic iPS-NKT cell monotherapy for advanced or recurrent HNC patients started to test the feasibility and safety of intra-arterial injection of iPS-NKT cells.Conclusions: The clinical study of allogenic iNKT cells is under evaluation. Once the safety profiles of iPS-NKT cell monotherapy are confirmed, we further plan to conduct a combination therapy with iPS-NKT cells plus αGalCer-pulsed APCs. Restimulated iPS-NKT cells are expected to exert potent adjuvant effects and improve anti-tumor responses.

著者

Hozumi Tashima Yuka Endo Naoto Okada Shingen Nakamura Kumiko Kagawa Shiro Fujii Hirokazu Miki Keisuke Ishizawa Masahiro Abe Youichi Sato

出版者

International Society of Personalized Medicne

雑誌

Personalized Medicine Universe (ISSN:21864969)

巻号頁・発行日

vol.10, pp.1-6, 2021-12-01 (Released:2022-01-07)

参考文献数

9

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Purpose: Cytarabine arabinoside (Ara-C) is an anti-metabolite that is commonly used as a therapeutic agent for acute leukemia; however, it can cause adverse drug reactions, such as digestive disorders, rashes, and fever. Therefore, identification of gene markers that can accurately predict the development of adverse drug reactions is useful for selecting effective drugs for therapy. After entering the cells, Ara-C is metabolized to Ara-C triphosphate, which inhibits DNA synthesis and exhibits antitumor activity. Therefore, we conducted an association study between the adverse reactions to cytarabine therapy and single nucleotide polymorphisms (SNPs) in cytarabine metabolic genes.Methods: Among the patients treated with cytarabine at the Department of Hematology at Tokushima University Hospital, 46 patients provided informed consent and were included in this study. We selected 14 tag SNPs located in nine genes that are involved in the cytarabine metabolic pathway; these SNPs were genotyped using the polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) technique. Association analyses between adverse reactions to Ara-C therapy and SNPs were performed using logistic regression analysis.Results: The rs9394992 polymorphism in the SLC29A1 gene and rs3886768 polymorphism in the DCTD gene were associated with the development of rash after Ara-C therapy. The rs7277 polymorphism in the DCTD gene was associated with fever, and the rs16945930 polymorphism in the ABCC11 gene was associated with sore throat.Conclusions: Our findings suggest that SNPs in the Ara-C metabolic genes influence the development of adverse reactions to Ara-C, and the results suggest that these genes can be predictive of adverse reactions to Ara-C therapy.

著者

Minako Abe Hiroyuki Abe

出版者

International Society of Personalized Medicne

雑誌

Personalized Medicine Universe (ISSN:21864969)

巻号頁・発行日

vol.9, pp.10-14, 2020-10-31 (Released:2020-12-01)

参考文献数

47

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Immune resilience is the ability for the human body to adapt and respond to adverse conditions, such as bacterial pathogens, viral infections, and abnormal or cancerous cells. Our ability to mount an appropriate response against such illness relates directly to our level of immune resilience, which in turn is impacted by our lifestyle choices. Nutrition, exercise, sleep and stress management are powerful influencers of mucosal immunity, the first line of defense against pathogens, and the exposome, exogenous and endogenous factors affecting our overall health. Lifestyle medicine offers evidence-based recommendations on how to optimize our immune system to withstand and thwart infections and disease.