Methods and products for determining responsiveness to anti-pd1 immune checkpoint inhibitor immunotherapy
AssigneesUniversity of South Australia, Central Adelaide Local Health Network Incorporated
InventorsLisa Michelle Ebert, Michael Paul Brown, Nga Thi Hong Truong
Life of this patent
Estimating the term…
Abstract
The present invention provides methods, systems, and kits for determining responsiveness of a subject with or susceptible to cancer to anti-PD1 immune checkpoint inhibitor immunotherapy (ICII) including determining the level of one or more of markers CD15 in CD8+Ki67/CD71+ or CD8/CD4−Ki67/CD71+ T cells, CTLA-4 in CD4+Ki67/CD71+ T cells, FoxP3 in CD4+Ki67/CD71+ T cells, Ki67 or CD71 in CD8+ T cells, wherein an increase in CD15, CTLA-4, FoxP3, or a decrease in Ki67 or CD71 prior to immunotherapy is indicative that the subject is responsive to immunotherapy, particularly PD1 ICII.
Claims36
A method of determining responsiveness of a subject suffering from, or susceptible to, a cancer to anti-PD1 immune checkpoint inhibitor immunotherapy, the method comprising assessing the vascular and/or tumour associated level in the subject of one or more of CD15s marker in Ki67+CD8+ T cells or CD71+CD8+ T cells, CTLA-4 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, FoxP3 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, CD15s marker in Ki67+CD4− CD8− T cells or CD71+CD4− CD8− T cells, and Ki67 marker in CD8+ T cells or CD71 marker in CD8+ T cells, wherein an increased level of the CD15s marker in the Ki67+CD8+ T cells or CD71+CD8+ T cells prior to the immunotherapy, an increased level of the CTLA-4 marker in said T cells prior to and/or after the immunotherapy, an increased level of the FoxP3 marker in said T cells prior to immunotherapy, an increased level of the CD15s marker in Ki67+CD4− CD8− T cells or CD71+CD4− CD8− T cells prior to immunotherapy, and a decreased level of the Ki67+ marker or CD71+ in said T cells prior to immunotherapy, is indicative that the subject is responsive to the immunotherapy.
A method of determining responsiveness of a subject suffering from, or susceptible to, a cancer to anti-PD1 immune checkpoint inhibitor immunotherapy, the method comprising assessing the level in the blood in the subject of one or more of CD15s marker in Ki67+CD8+ T cells or CD71+CD8+ T cells, CTLA-4 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, FoxP3 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, CD15s marker in Ki67+CD4− CD8− T cells or CD71+CD4− CD8− T cells, and Ki67 marker or CD71 marker in CD8+ T cells, wherein an increased level of the CD15s marker in the Ki67+CD8+ T cells or CD71+CD8+ T cells prior to the immunotherapy, an increased level of the CTLA-4 marker in said T cells prior to and/or after the immunotherapy, an increased level of the FoxP3 marker in said T cells prior to immunotherapy, an increased level of the CD15s marker in Ki67+CD4− CD8− T cells or CD71+CD4− CD8− T cells prior to immunotherapy, and a decreased level of the Ki67+ marker or CD71 marker in said T cells prior to immunotherapy, is indicative that the subject is responsive to the immunotherapy.
A method of determining responsiveness of a subject suffering from, or susceptible to, a cancer to anti-PD1 immune checkpoint inhibitor immunotherapy, the method comprising assessing the level in cells in a tumour in the subject of one or more of CD15s marker in Ki67+CD8+ T cells or CD71+CD8+ T cells, CTLA-4 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, FoxP3 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, CD15s marker in Ki67+CD4− CD8− T cells or CD71+CD4− CD8− T cells, and Ki67 marker or CD71 marker in CD8+ T cells, wherein an increased level of the CD15s marker in the Ki67+CD8+ T cells or CD71+CD8+ T cells prior to the immunotherapy, an increased level of the CTLA-4 marker in said T cells prior to and/or after the immunotherapy, an increased level of the FoxP3 marker in said T cells prior to immunotherapy, an increased level of the CD15s marker in Ki67+CD4− CD8− T cells or CD71+CD4− CD8− T cells prior to immunotherapy, and a decreased level of the Ki67+ marker or CD71 marker in said T cells prior to immunotherapy, is indicative that the subject is responsive to the immunotherapy.
A method of determining responsiveness of a subject suffering from, or susceptible to, a cancer to anti-PD1 immune checkpoint inhibitor immunotherapy, the method comprising assessing the level in tumour infiltrating lymphocytes in the subject of one or more of CD15s marker in Ki67+CD8+ T cells or CD71+CD8+ T cells, CTLA-4 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, FoxP3 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, CD15s marker in Ki67+CD4− CD8− T cells or CD71+CD4− CD8− T cells, and Ki67 marker or CD71 marker in CD8+ T cells, wherein an increased level of the CD15s marker in the Ki67+CD8+ T cells or CD71+CD8+ T cells prior to the immunotherapy, an increased level of the CTLA-4 marker in said T cells prior to and/or after the immunotherapy, an increased level of the FoxP3 marker in said T cells prior to immunotherapy, an increased level of the CD15s marker in Ki67+CD4− CD8− T cells or CD71+CD4− CD8− T cells prior to immunotherapy, and a decreased level of the Ki67+ marker or CD71 marker in said T cells prior to immunotherapy, is indicative that the subject is responsive to the immunotherapy.
A method of treating a subject suffering from, or susceptible to, a cancer with an anti-PD1 immune checkpoint inhibitor immunotherapy, the method comprising:
- determining responsiveness of the subject to the immune checkpoint inhibitor immunotherapy on the basis of the vascular and/or tumour associated level of one or more of CD15s marker in Ki67+CD8+ T cells or CD71+CD8+ T cells, CTLA-4 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, FoxP3 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, CD15s marker in Ki67+CD4− CD8− T cells or CD71+CD4− CD8− T cells, and Ki67 marker or CD71 marker in CD8+ T cells, wherein an increased level of the CD15s marker in the Ki67+CD8+ T cells or CD71+CD8+ T cells prior to the immunotherapy, an increased level of the CTLA-4 marker in said T cells prior to and/or after the immunotherapy, an increased level of the FoxP3 marker in said T cells prior to immunotherapy, an increased level of the CD15s marker in Ki67+CD4− CD8− T cells or CD71+CD4− CD8− T cells prior to immunotherapy, and a decreased level of the Ki67+ marker or CD71 marker in said T cells prior to immunotherapy, is indicative that the subject is responsive to the immunotherapy;
- and
- treating the subject determined to be responsive with the immunotherapy.
A kit for use in assessing responsiveness of a subject suffering from, or susceptible to, a cancer to anti-PD1 immune checkpoint inhibitor immunotherapy;
- the kit comprising one or more of an immunological reagent for detecting CD15s marker, an immunological reagent for detecting CTLA-4 marker, an immunological reagent for detecting FoxP3 marker, and one or both of an immunological reagent for detecting Ki67 and an immunological reagent for detecting CD71.
Use of one or more of CD15s, CTLA-4, FoxP3, Ki67 and CD71 as a marker to assess the responsiveness of a subject suffering from, or susceptible to, a cancer to anti-PD1 immune checkpoint inhibitor immunotherapy.
A method of assessing responsiveness of a subject suffering from, or susceptible to, a cancer to anti-PD1 immune checkpoint inhibitor immunotherapy, the method comprising:
- receiving data representative of the vascular and/or tumour associated level of one or more of CD15s marker in Ki67+CD8+ T cells or CD71+CD8+ T cells, CTLA-4 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, FoxP3 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, CD15s marker in Ki67+CD4− CD8− T cells or CD71+CD4− CD8− T cells, Ki67 in CD8+ T cells and CD71 in CD8+ T cells;
- and
- processing the data to determine the responsiveness of the subject to the immunotherapy.
A system for assessing responsiveness of a subject suffering from, or susceptible to, a cancer to anti-PD1 immune checkpoint inhibitor immunotherapy, the system comprising
- a means for determining the level of one or more of CD15s marker in Ki67+CD8+ T cells or CD71+CD8+ T cells, CTLA-4 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, FoxP3 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, CD15s marker in Ki67+CD4− CD8− T cells or CD71+CD4− CD8− T cells, Ki67 in CD8+ T cells and CD71 in CD8+ T cells, in a blood and/or tumour associated sample from a subject;
- a processor;
- a memory;
- and
- software resident in the memory accessible to the processor, the software comprising a series of instructions executable by the processor to process data representative of the vascular and/or tumour associated level of the one or more of the markers, and thereby provide a measure of the responsiveness of the subject to the immunotherapy.
A system for assessing responsiveness of a subject suffering from, or susceptible to, a cancer to anti-PD1 immune checkpoint inhibitor immunotherapy, the system comprising
- a flow cytometer;
- a processor;
- a memory;
- and
- software resident in the memory accessible to the processor, the software comprising a series of instructions executable by the processor to process data received from the flow cytometer representative of the vascular and/or tumour associated level of the CD15s marker in Ki67+CD8+ T cells or CD71+CD8+ T cells, CTLA-4 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, FoxP3 marker in Ki67+CD4+ T cells or CD71+CD4+ T cells, CD15s marker in Ki67+CD4− CD8− T cells or CD71+CD4− CD8− T cells, Ki67 in CD8+ T cells and CD71 in CD8+ T cells, and thereby provide a measure of the responsiveness of the subject to the immunotherapy.
Dependencies are inferred from the claim text.