Calabasas, CA, United States
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Ji J.,Cedars Sinai Medical Center | Judkowski V.A.,Torrey Pines Institute for Molecular Studies | Liu G.,Cedars Sinai Medical Center | Wang H.,Cedars Sinai Medical Center | And 7 more authors.
Stem Cells Translational Medicine | Year: 2014

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. © AlphaMed Press 2014.


Phuphanich S.,Cedars Sinai Medical Center | Wheeler C.J.,Cedars Sinai Medical Center | Rudnick J.D.,Cedars Sinai Medical Center | Mazer M.,Cedars Sinai Medical Center | And 12 more authors.
Cancer Immunology, Immunotherapy | Year: 2013

Background: This study evaluated the safety and immune responses to an autologous dendritic cell vaccine pulsed with class I peptides from tumor-associated antigens (TAA) expressed on gliomas and overexpressed in their cancer stem cell population (ICT-107). Methods: TAA epitopes included HER2, TRP-2, gp100, MAGE-1, IL13Rα2, and AIM-2. HLA-A1- and/or HLA-A2-positive patients with glioblastoma (GBM) were eligible. Mononuclear cells from leukapheresis were differentiated into dendritic cells, pulsed with TAA peptides, and administered intradermally three times at two-week intervals. Results: Twenty-one patients were enrolled with 17 newly diagnosed (ND-GBM) and three recurrent GBM patients and one brainstem glioma. Immune response data on 15 newly diagnosed patients showed 33 % responders. TAA expression by qRT-PCR from fresh-frozen tumor samples showed all patient tumors expressed at least three TAA, with 75 % expressing all six. Correlations of increased PFS and OS with quantitative expression of MAGE1 and AIM-2 were observed, and a trend for longer survival was observed with gp100 and HER2 antigens. Target antigens gp100, HER1, and IL13Rα2 were downregulated in recurrent tumors from 4 HLA-A2+ patients. A decrease in or absence of CD133 expression was seen in five patients who underwent a second resection. At a median follow-up of 40.1 months, six of 16 ND-GBM patients showed no evidence of tumor recurrence. Median PFS in newly diagnosed patients was 16.9 months, and median OS was 38.4 months. Conclusions: Expression of four ICT-107 targeted antigens in the pre-vaccine tumors correlated with prolonged overall survival and PFS in ND-GBM patients. The goal of targeting tumor antigens highly expressed on glioblastoma cancer stem cells is supported by the observation of decreased or absent CD133 expression in the recurrent areas of gadolinium-enhanced tumors. © 2012 The Author(s).


Patent
Immunocellular Therapeutics Ltd. and Cedars Sinai Medical Center | Date: 2014-02-14

Compositions of multipeptide vaccines including tumor associated antigens, compositions of antigen presenting cell (e.g., dendritic cell) based vaccines presenting epitopes from tumor associated antigens, and methods of making same, are provided herein. Also, disclosed are methods for treating ovarian cancers using such vaccines.


Patent
Immunocellular Therapeutics Ltd | Date: 2014-02-14

Compositions of multipeptide vaccines comprising at least seven tumor associated antigens, compositions of antigen presenting cell (e.g., dendritic cell) based vaccines presenting epitopes from at least seven tumor associated antigens, and methods of making same, are provided herein. Also, disclosed are methods for treating gynecological and peritoneal cancers using such vaccines.


Patent
Cedars Sinai Medical Center and ImmunoCellular Therapeutics Ltd. | Date: 2014-02-14

Compositions of multipeptide vaccines including tumor associated antigens, compositions of antigen presenting cell (e.g., dendritic cell) based vaccines presenting epitopes from tumor associated antigens, and methods of making same, are provided herein. Also, disclosed are methods for treating ovarian cancers using such vaccines.


Patent
ImmunoCellular Therapeutics Ltd. | Date: 2014-02-14

Compositions of multipeptide vaccines comprising at least seven tumor associated antigens, compositions of antigen presenting cell (e.g., dendritic cell) based vaccines presenting epitopes from at least seven tumor associated antigens, and methods of making same, are provided herein. Also, disclosed are methods for treating gynecological and peritoneal cancers using such vaccines.


Patent
Immunocellular Therapeutics Ltd. | Date: 2013-01-09

An immunogen includes an isolated peptide that includes the amino sequence of any one of SEQ ID NOs:1-21 with four or fewer amino acid substitutions.


PubMed | ImmunoCellular Therapeutics Ltd., Cedars Sinai, Torrey Pines Institute for Molecular Studies and ZellNet Consulting
Type: Published Erratum | Journal: Cells | Year: 2015

The authors wish to make the following corrections to this paper [1]: [...].

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