PMID- 24375541 OWN - NLM STAT- MEDLINE DCOM- 20140513 LR - 20231120 IS - 2157-6564 (Print) IS - 2157-6580 (Electronic) IS - 2157-6564 (Linking) VI - 3 IP - 3 DP - 2014 Mar TI - Identification of novel human leukocyte antigen-A*0201-restricted, cytotoxic T lymphocyte epitopes on CD133 for cancer stem cell immunotherapy. PG - 356-64 LID - 10.5966/sctm.2013-0135 [doi] AB - Targeting cancer stem cells (CSCs) with immunotherapy may be an effective means to prevent recurrences in glioblastoma multiforme (GBM). It is well established that CD133 is expressed in the population of GBM tumor cells representing CSCs. This raises a possibility that CD133 could serve as a potential target for cytotoxic T cells (CTLs) to target glioblastoma cancer stem cells. Two potential human leukocyte antigen (HLA)-A*0201-restricted CD133 epitopes, ILSAFSVYV (CD133-405) and YLQWIEFSI (CD133-753), showed strong binding to HLA-A*0201 molecules. In vitro immunogenicity studies generated peptide-specific CD8(+) CTLs from normal donors. Autologous monocyte-derived dendritic cells pulsed with the CD133-405 or CD133-753 peptides generated CTLs that efficiently recognized the CD133 epitopes presented in T2 HLA-A*0201 cells and specifically lysed CD133+ HLA-A*0201(+) GBM CSCs. These studies demonstrated natural processing and subsequent presentation of these epitopes in GBM CSCs and the ability of CTLs to kill CSCs bearing the antigen. Immunization studies in mice using the mouse homolog CD133 epitopes demonstrated immunogenicity in the absence of autoimmune damage. The results presented in this study support the use of CD133-specific epitope vaccines to target CSCs in glioblastoma and other cancers. FAU - Ji, Jianfei AU - Ji J AD - Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA; Torrey Pines Institute for Molecular Studies, San Diego, California, USA; ImmunoCellular Therapeutics, Ltd., Calabasas, Calfornia, USA. FAU - Judkowski, Valeria A AU - Judkowski VA FAU - Liu, Gentao AU - Liu G FAU - Wang, Hongqiang AU - Wang H FAU - Bunying, Alcinette AU - Bunying A FAU - Li, Zhenhua AU - Li Z FAU - Xu, Minlin AU - Xu M FAU - Bender, James AU - Bender J FAU - Pinilla, Clemencia AU - Pinilla C FAU - Yu, John S AU - Yu JS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131227 PL - England TA - Stem Cells Transl Med JT - Stem cells translational medicine JID - 101578022 RN - 0 (AC133 Antigen) RN - 0 (Antigens, CD) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (Glycoproteins) RN - 0 (HLA-A*02:01 antigen) RN - 0 (HLA-A2 Antigen) RN - 0 (Oligopeptides) RN - 0 (PROM1 protein, human) RN - 0 (Peptides) RN - 0 (Prom1 protein, mouse) SB - IM MH - AC133 Antigen MH - Animals MH - Antigens, CD/genetics/*immunology MH - Cell- and Tissue-Based Therapy MH - Central Nervous System Neoplasms/genetics/immunology/pathology/*therapy MH - Cytotoxicity, Immunologic MH - Dendritic Cells/cytology/drug effects/immunology MH - Epitopes, T-Lymphocyte/genetics/*immunology MH - Gene Expression/immunology MH - Glioblastoma/genetics/immunology/pathology/*therapy MH - Glycoproteins/genetics/*immunology MH - HLA-A2 Antigen/genetics/*immunology MH - Humans MH - Immunotherapy/*methods MH - Mice MH - Neoplastic Stem Cells/drug effects/*immunology/pathology MH - Oligopeptides/chemical synthesis/immunology/pharmacology MH - Peptides/genetics/*immunology MH - Protein Binding MH - Secondary Prevention MH - T-Lymphocytes, Cytotoxic/cytology/drug effects/*immunology PMC - PMC3952931 OTO - NOTNLM OT - CD133 OT - Cancer stem cell OT - Cytotoxic T cell OT - Dendritic cell OT - Immunotherapy EDAT- 2014/01/01 06:00 MHDA- 2014/05/14 06:00 PMCR- 2015/03/01 CRDT- 2013/12/31 06:00 PHST- 2013/12/31 06:00 [entrez] PHST- 2014/01/01 06:00 [pubmed] PHST- 2014/05/14 06:00 [medline] PHST- 2015/03/01 00:00 [pmc-release] AID - sctm.2013-0135 [pii] AID - 130135 [pii] AID - 10.5966/sctm.2013-0135 [doi] PST - ppublish SO - Stem Cells Transl Med. 2014 Mar;3(3):356-64. doi: 10.5966/sctm.2013-0135. Epub 2013 Dec 27.