Identification of Novel Human Leukocyte Antigen-A*0201-Restricted, Cytotoxic T Lymphocyte Epitopes on CD133 for Cancer Stem Cell Immunotherapy

Abstract

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.

Concise Reviews: Cancer Stem Cells: From Concept to Cure

“…Immunization of mice with the murine homologs of the CD133 epitopes demonstrated immunogenicity in the absence of autoimmune damage. The study supports the use of CD133‐specific epitope vaccines to target CSCs in glioblastoma, and argues for a clinical trial to assess the safety of this approach .…”

Peptide vaccination therapy: Towards the next generation

“…Recently, the potentials of immunotherapy targeting CSC antigens has been demonstrated by Ji et al who reported the usefulness of CD133‐derived epitopes in the context of HLA‐A2 to induce CTLs to reject glioblastoma. The number of CSCs/CICs is very low compared with the other populations, so they might be efficiently rejected by the limited number of peptide‐specific CTLs in vivo . Dillman et al also suggested the potentials of CSC antigen‐based vaccines for melanoma …”

“…The number of CSCs/CICs is very low compared with the other populations, so they might be efficiently rejected by the limited number of peptide-specific CTLs in vivo. 62 Dillman et al also suggested the potentials of CSC antigen-based vaccines for melanoma. 63 On the other hand, it is hard to eradicate a large tumor burden by peptide vaccination alone.…”

Stem cell in alternative treatments for brain tumors: potential for gene delivery

“…This particular subpopulation of cells is therefore the ideal candidate for vaccine therapy. Ji et al took advantage of CD133, a proposed marker of gCSCs, as a target to stimulate cytotoxic T-cells (CTLs) [ 69 ]. Peptide-specific CD8 + CTLs from normal donors were generated and pulsed with autologous DCs.…”