CRISPR-based gene disruption coupled to targeted integration of novel, high-avidity, natural T cell receptors to WT1 for acute leukemia
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE189518 | GEO | 2022/02/09
REPOSITORIES: GEO
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Project description:To better characterize and identify the candidate TCR among the receptors that we have isolated, we dissected the gene expression profiles and biological pathways of HD1- and HD3-TCR edited T cells by single cell sequencing. When challenged with target cells (either WT137-45- pulsed T2 cell line or primary AML blasts), results highlighted an immune response gene signature in each stimulated T cell culture, compared to resting counterparts. Interestingly, upregulation of genes mediating IFNa and g response, T cell proliferation and CD4+ T cell activation was observed in HD1- but not in HD3-TCR T cells stimulated with primary leukemic blasts.
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Project description:CRISPR-based gene disruption coupled to targeted integration of novel, high-avidity, natural T cell receptors to WT1 for acute leukemia
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Project description:CRISPR-based gene disruption coupled to targeted integration of novel, high-avidity, natural T cell receptors to WT1 for acute leukemia
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Primary outcome(s): Induction of WT1-specific immune responses assessed by WT1-related tests such as WT1-DTH skin reaction and serum levels of WT1 peptide IgG autoantibody at 1M, 2M, and 3M of WT1 Trio vaccine.
Study Design: Single arm Non-randomized
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Project description:Interventions: A patient is vaccinated with Montanide ISA51-adjuvanted WT1 Trio cancer vaccine consisting of two WT1 CTL peptides (WT1-126 and WT1-235) and one WT1 HTL peptide (WT1-332) (2mg each) seven times at the interval of two to four weeks. The interval can be changed within a range from one to 16 weeks.
Primary outcome(s): Induction of WT1-specific immune responses assessed by WT1-related tests such as WT1-DTH skin reaction, serum levels of WT1 peptide IgG autoantibody, and frequency of WT1-CTL in PB * This is evaluated at the interval ranging from 6 to 12 months.
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