PMID- 30760061 OWN - NLM STAT- MEDLINE DCOM- 20200306 LR - 20200306 IS - 1750-7448 (Electronic) IS - 1750-743X (Linking) VI - 11 IP - 6 DP - 2019 Apr TI - Delayed IL-21 treatment preferentially expands peptide-specific CD8(+) T cells by reducing bystander activation of T cells. PG - 497-513 LID - 10.2217/imt-2018-0095 [doi] AB - AIM: We previously reported a simple and practical procedure to generate peptide-specific CD8(+) T cells using peptide and IL-2, which is applied to produce human telomerase reverse transcriptase (hTERT)-specific CD8+ T cells for clinical use. We have modified the procedure to enhance the amplification of peptide-specific CD8(+) T cells adding IL-21. MATERIALS & METHODS: Using human leukocyte antigen (HLA)-A*0201-restricted cytomegalovirus/pp65-specific CD8(+) T cells of healthy volunteers, we optimized the culture conditions by adjusting the dose and timing of IL-21 treatment. RESULTS & CONCLUSION: By adding IL-21, we accelerated the expansion rate of cytomegalovirus/pp65-specific CD8(+) T cells by reducing bystander activation of T cells. We expect that the procedure including IL-21 would improve the production rate of hTERT- and Wilms tumor 1 (WT1)-specific CD8(+) T cells for clinical trials. FAU - Kim, Seon-Hee AU - Kim SH AD - Immunotherapeutics Branch, Division of Convergence Technology, National Cancer Center, Goyang, 10408 Korea. FAU - Park, Sang-Yoon AU - Park SY AD - Common Cancer Branch, Division of Clinical Research, National Cancer Center, Goyang, 10408 Korea. AD - Center for Uterine Cancer, National Cancer Center, Goyang, 10408 Korea. FAU - Lim, Myong Cheol AU - Lim MC AD - Center for Uterine Cancer, National Cancer Center, Goyang, 10408 Korea. AD - Cancer Healthcare Research Branch, Division of Cancer Epidemiology & Management, National Cancer Center, Goyang, 10408 Korea. FAU - Lee, Eun Sook AU - Lee ES AD - Immunotherapeutics Branch, Division of Convergence Technology, National Cancer Center, Goyang, 10408 Korea. AD - Center for Breast Cancer, National Cancer Center, Goyang, 10408 Korea. FAU - Lee, Eun Gyeong AU - Lee EG AD - Center for Breast Cancer, National Cancer Center, Goyang, 10408 Korea. FAU - Han, Seoung-Eun AU - Han SE AD - Immunotherapeutics Branch, Division of Convergence Technology, National Cancer Center, Goyang, 10408 Korea. FAU - Kim, Young-Ho AU - Kim YH AD - Rare Cancer Branch, Division of Clinical Research, National Cancer Center, Goyang, 10408, Korea. FAU - Kwon, Byoung S AU - Kwon BS AD - Eutilex, Co., Ltd, Suite# 1401 Daeryung Technotown 17 Gasan digital 1-ro 25, Geumcheon-gu, Seoul 08594, Korea. AD - Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA Center for Breast Cancer, National Cancer Center, Goyang, 10408 Korea. FAU - Choi, Beom K AU - Choi BK AD - Biomedicine Production Branch, National Cancer Center, Goyang, 10408 Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190214 PL - England TA - Immunotherapy JT - Immunotherapy JID - 101485158 RN - 0 (Antigens, Neoplasm) RN - 0 (HLA-A*02:01 antigen) RN - 0 (HLA-A2 Antigen) RN - 0 (Interleukins) RN - 0 (Peptides) RN - 0 (Viral Matrix Proteins) RN - 0 (cytomegalovirus matrix protein 65kDa) RN - MKM3CA6LT1 (interleukin-21) SB - IM MH - Antigens, Neoplasm/immunology MH - Bystander Effect MH - CD8-Positive T-Lymphocytes/*immunology MH - Cell Proliferation MH - Cells, Cultured MH - HLA-A2 Antigen/metabolism MH - Humans MH - Immunotherapy, Adoptive/*methods MH - Interleukins/*metabolism MH - Lymphocyte Activation MH - Neoplasms/immunology/*therapy MH - Peptides/immunology/metabolism MH - Protein Binding MH - T-Cell Antigen Receptor Specificity MH - Viral Matrix Proteins/immunology/metabolism OTO - NOTNLM OT - 4-1BB OT - CD137 OT - CD8 T cells OT - IL-21 OT - immunotherapy OT - tumor-associated antigen EDAT- 2019/02/15 06:00 MHDA- 2020/03/07 06:00 CRDT- 2019/02/15 06:00 PHST- 2019/02/15 06:00 [pubmed] PHST- 2020/03/07 06:00 [medline] PHST- 2019/02/15 06:00 [entrez] AID - 10.2217/imt-2018-0095 [doi] PST - ppublish SO - Immunotherapy. 2019 Apr;11(6):497-513. doi: 10.2217/imt-2018-0095. Epub 2019 Feb 14.