Method of selecting WT1 vaccine adaptive patient
AssigneeInternational Institute of Cancer Immunology, Inc.
InventorHaruo Sugiyama
Life of this patent
Estimating the term…
Abstract
A method of selecting patients highly responsive to WT1 vaccine and a therapeutic method for treating cancer involving said method of selection are provided, which method of selecting patients highly responsive to WT1 vaccine comprises: (a) isolating a biological sample containing CTL precursor cells from a test subject; (b) measuring the existence frequency or amount of WT1-specific CTL precursor cells in the biological sample of (a); and (c) deciding whether or not the measured value of (b) is high by comparison with that of healthy subject, and evaluating the responsiveness to WT1 vaccine.
Claims16
A method of selecting a cancer patient highly responsive to WT1 vaccine and treating the patient, comprising:
- (a) isolating PBMCs or blood containing CTL precursor cells from a cancer patient who has not been previously immunized with WT1 vaccine;
- (b) contacting the PBMCs or blood of (a) with an HLA tetramer comprising a peptide, wherein the HLA tetramer is an HLA-A2 tetramer comprising a peptide comprising the amino acid sequence of SEQ ID NO:
- 4, or an HLA-A24 tetramer comprising a peptide comprising the amino acid sequence of SEQ ID NO:
- 2 or 3,
- (c) determining the number of CD8+CD45RA+CD27− CTL precursor cells bound to any one of the HLA tetramers relative to the number of CD8+ CTL precursor cells bound to the same HLA tetramer, and
- (d) administering a WT1 vaccine to a cancer patient who has a ratio of CD8+CD45RA+CD27− to CD8+ cells as determined in (c) that is significantly higher, as defined by a p value of <0.05, than the ratio of CD8+CD45RA+CD27− CTL precursor cells to CD8+ CTL precursor cells which bind the same tetramer as in (c) contained within the PBMCs or blood of a control subject who does not have cancer,
- wherein the WT1 vaccine comprises at least one WT1-derived cancer antigen peptide selected from the group consisting of:
- (SEQ ID NO:
- 2)
- Cys Met Thr Trp Asn Gln Met Asn Leu,
- (SEQ ID NO:
- 3)
- Cys Tyr Thr Trp Asn Gln Met Asn Leu,
- and
- (SEQ ID NO:
- 4)
- Arg Met Phe Pro Asn Ala Pro Tyr Leu.
A method of selecting a cancer patient highly responsive to a WT1 vaccine and treating the selected patient, comprising:
- (a) isolating a PBMCs or blood comprising CTL precursor cells from a cancer patient who has not been previously immunized with a WT1 vaccine;
- (b) contacting the PBMCs or blood of (a) with an HLA tetramer comprising a peptide, wherein the HLA tetramer is an HLA-A2 tetramer comprising a peptide comprising the amino acid sequence of SEQ ID NO:
- 4, or an HLA-A24 tetramer comprising a peptide comprising the amino acid sequence of SEQ ID NO:
- 2 or 3,
- (c) determining the number of CD8+CD45RA+CD27− CTL precursor cells bound to any one of the HLA tetramers relative to the number of CD8+ CTL precursor cells bound to the same HLA tetramer,
- wherein the determining in (c) comprises:
- contacting the PBMCs or blood with the HLA tetramer and with an anti-CD8 antibody, an anti-CD45RA antibody, and an anti-CD27 antibody, and
- (d) identifying a cancer patient who has a ratio of CD8+CD45RA+CD27− to CD8+ cells as determined in (c) that is significantly higher, as defined by a p value of <0.05, than the ratio of CD8+CD45RA+CD27− CTL precursor cells to CD8+ CTL precursor cells which bind the same tetramer as in (c) contained within the PBMCs or blood of a control subject who does not have cancer, and
- administering the WT1 vaccine to the identified cancer patient,
- wherein the WT1 vaccine comprises at least one WT1-derived cancer antigen peptide selected from the group consisting of:
- (SEQ ID NO:
- 2)
- Cys Met Thr Trp Asn Gln Met Asn Leu,
- (SEQ ID NO:
- 3)
- Cys Tyr Thr Trp Asn Gln Met Asn Leu,
- and
- (SEQ ID NO:
- 4)
- Arg Met Phe Pro Asn Ala Pro Tyr Leu.
Dependencies are inferred from the claim text.