Pvrl2 and/or pvrig as biomarkers for treatment
OwnerGad S. COJOCARU, Tal Fridman KFIR +7inventors
InventorsGad S. COJOCARU, Tal Fridman KFIR, Emmanuel WEYL, Amit NOVIK, Yossef KLIGER, Niv SABATH, Eran OPHIR, Zoya ALTEBER, Masha FRENKEL
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Abstract
The present invention provides biomarkers for use in determining populations for treatment with anti-PVRIG antibodies and such biomarkers include, for example PVRIG and/or PVRL2 expression.
Claims193
A method for determining a cancer patient population for treatment with an anti-PVRIG antibody, the method comprising:
- (a) detecting the presence in a biological sample from the cancer patient one or more cellular components selected from the group consisting of:
- (i) TSCM, TRM, naïve, exhausted, cycling, and effector CD8 positive T cells, that express PVRIG;
- and/or
- (ii) activated DC cells, DC1, and/or DC2 that express PVRL2,
- (b) quantitating the measurement of the level of components selected from the group consisting of:
- (i) TSCM, TRM, naïve, exhausted, cycling, and effector CD8 positive T cells, that express PVRIG;
- and/or
- (ii) activated DC cells, DC1, and/or DC2 that express PVRL2;
- and
- (c) treating the cancer patient with an anti-PVRIG antibody when one or more cellular components in (a) as quantitated in step (b) are present at an increased level as compared to a control or a patient that does not have detectable levels of the cells.
A method for predicting or determining the efficacy of treatment with an anti-PVRIG treatment antibody, the method comprising:
- (a) measuring the level of one or more cellular components selected from the group consisting of:
- (i) TSCM, TRM, naïve, exhausted, cycling, and effector CD8 positive T cells that express PVRIG;
- and/or
- (ii) activated DC cells, DC1, and DC2 that express PVRL2;
- (b) quantitating the measurement of the level of one or more cellular components selected from the group consisting of:
- (i) TSCM, TRM, naïve, exhausted, cycling, and effector CD8 positive T cells, expressing PVRIG;
- and/or
- (ii) activated DC cells, DC1, and DC2 that express PVRL2;
- and
- (c) correlating the level of the cellular components with the efficacy of treatment, wherein any of the cellular components being present and/or being present at an increased level as compared to a control or a patient that does not have detectable levels of the cells, is indicative of treatment efficacy for treatment with an anti-PVRIG treatment antibody.
A method for predicting or determining the efficacy of treatment or determining a population for treatment with an anti-PVRIG treatment antibody when any of TSCM, TRM, naïve, exhausted, cycling, and effector CD8 positive T cells, that express PVRIG comprise at least 0.5%, at least 1%, at least 1.5%, at least 2%, at least 2.5%, at least 3%, at least 3.5%, at least 4%, at least 4.5%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, or at least 85%, of the total CD8 cells in the biological sample is indicative of treatment efficacy and/or indicative for treatment with an anti-PVRIG antibody.
A method for predicting or determining the efficacy of treatment or determining a population for treatment with an anti-PVRIG treatment antibody when any of activated DC cells, DC1, and DC2 that express the PVRL2 comprise at least 0.1%, at least 0.2%, at least 0.3%, at least 0.4%, at least 0.5%, at least 0.6%, at least 0.7%, at least 0.8%, at least 0.9%, at least 1%, at least 1.5%, at least 2%, at least 2.5%, at least 3%, at least 3.5%, at least 4%, at least 4.5%, or at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, or at least 30%, out of total myeloid cells in the biological sample.
A method for predicting or determining the efficacy of treatment with an anti-PVRIG treatment antibody, the method comprising:
- (a) measuring the level of early memory CD8 T cells;
- (b) quantitating the measurement of the level of early memory CD8 T cells;
- (c) correlating the level of the early memory CD8 T cells with the efficacy of treatment.
A method for determining a cancer patient population for treatment with an anti-PVRIG treatment antibody, the method comprising:
- (a) measuring the level of PVRIG and/or PVRL2 expression in a biological sample obtained from a cancer and/or tumor microenvironment and/or peripheral blood in the cancer patient,
- (b) quantitating the measurement of the level of PVRIG and/or PVRL2 expression in the biological sample, and
- (c) treating the cancer patient with an anti-PVRIG antibody wherein PVRIG and/or PVRL2 is expressed and/or expressed at an increased level as compared to a control or a patient that does not have detectable levels of the PVRIG and/or PVRL2 in the biological sample.
A method for predicting or determining the efficacy of treatment with an anti-PVRIG treatment antibody, the method comprising:
- (a) measuring the level of PVRIG and/or PVRL2 expression in a biological sample obtained from a cancer and/or tumor microenvironment and/or peripheral blood in the cancer patient,
- (b) quantitating the measurement of the level of PVRIG and/or PVRL2 expression in the biological sample, and
- (c) correlating the level of PVRIG and/or PVRL2 with the efficacy of treatment, wherein PVRIG and/or PVRL2 is expressed and/or expressed at an increased level as compared to a control or a patient that does not have detectable levels of the PVRIG and/or PVRL2, is indicative of treatment efficacy for treatment with an anti-PVRIG treatment antibody.
A method for determining a cancer patient population for treatment with an anti-PVRIG antibody, the method comprising:
- (a) detecting the presence in a biological sample from the cancer patient early memory CD8 T cells;
- (b) quantitating the measurement of the level of early memory CD8 T cells;
- (c) treating the cancer patient with an anti-PVRIG antibody when the level of early memory CD8 T cells are present at an increased level as compared to a control or a patient that does not have detectable levels of the cells.
A method for altering the regimen of treatment for a patient with cancer, the method comprising:
- (a) measuring the level of PVRIG and/or PVRL2 expression in a biological sample obtained from a cancer and/or tumor microenvironment and/or peripheral blood in the cancer patient,
- (b) quantitating the measurement of the level of PVRIG and/or PVRL2 expression in the biological sample, wherein PVRIG and/or PVRL2 being expressed and/or being expressed at an increased level as compared to a control or a patient that does not have detectable levels of the PVRIG and/or PVRL2 is indicative of treatment efficacy,
- (c) correlating the level of PVRIG and/or PVRL2 expression with the efficacy of treatment, wherein a high level of PVRIG and/or PVRL2 expression is indicative of altering the treatment regimen for treatment with anti-PVRIG treatment antibody, and
- (d) altering the treatment regimen to include an anti-PVRIG antibody when a moderate or high level of PVRIG and/or PVRL2 expression is measured.
The method according to 18, wherein the single-cell resolution analysis includes RNAseq, immunohistochemistry (IHC), multiplex immunohistochemistry (mIHC) and/or immunofluorescence (IF), flow cytometry (e.g., FACS) and mass cytometry (e.g., CyTOF), as well as combinations thereof.
An agent for use in a method, including a method of treatment, wherein the agent is capable of blocking the interaction between PVRIG and PVRL2.
A method for determining a cancer patient population for treatment with an anti-PVRIG antibody, the method comprising:
- (d) detecting the presence of DNAM-1 and/or PVRIG in a biological sample from the cancer patient;
- (e) quantitating the measurement of the level of DNAM-1 and/or PVRIG;
- and
- (f) treating the cancer patient with an anti-PVRIG antibody when PVRIG in (a) as quantitated in step (b) are present and/or present at an increased level as compared to a control or a patient that does not have detectable levels of DNAM-1 and/or PVRIG.
A method for predicting or determining the efficacy of treatment for a cancer patient with an anti-PVRIG treatment antibody, the method comprising:
- (a) measuring the level of DNAM-1 and/or PVRIG;
- (b) quantitating the measurement of the level of DNAM-1 and/or PVRIG;
- and
- (c) correlating the level of the DNAM-1 and/or PVRIG with the efficacy of treatment, wherein any of DNAM-1 and/or PVRIG being present and/or being present at an increased level as compared to a control or a patient that does not have detectable levels of DNAM-1 and/or PVRIG, is indicative of treatment efficacy for treatment with an anti-PVRIG treatment antibody.
A method for predicting or determining the efficacy of treatment or determining a population for treatment with an anti-PVRIG treatment antibody when the immune cells that express DNAM-1 and/or PVRIG comprise at least 0.1%, at least 0.5%, at least 1%, at least 1.5%, at least 2%, at least 2.5%, at least 3%, at least 3.5%, at least 4%, at least 4.5%, at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, or at least 85% of the total immune cells in the biological sample is indicative of treatment efficacy and/or indicative for treatment with an anti-PVRIG antibody.
A method for predicting or determining the efficacy of treatment or determining a population for treatment with an anti-PVRIG treatment antibody when the T cells, NK cells, and NKT cells in the immune cells that express DNAM-1 and/or PVRIG comprise at least 0.1%, at least 0.2%, at least 0.3%, at least 0.4%, at least 0.5%, at least 0.6%, at least 0.7%, at least 0.8%, at least 0.9%, at least 1%, at least 1.5%, at least 2%, at least 2.5%, at least 3%, at least 3.5%, at least 4%, at least 4.5%, or at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, or at least 30%, out of total T cells, NK cells, and NKT cells in the biological sample is indicative of treatment efficacy and/or indicative for treatment with an anti-PVRIG antibody.
A method for determining a cancer patient population for treatment with an anti-PVRIG treatment antibody, the method comprising:
- (a) measuring the level of PVRIG and/or DNAM-1 expression in a biological sample obtained from a cancer and/or tumor microenvironment and/or peripheral blood in the cancer patient,
- (b) quantitating the measurement of the level of PVRIG and/or DNAM-1 expression in the biological sample, and
- (c) treating the cancer patient with an anti-PVRIG antibody wherein PVRIG and/or DNAM-1 is expressed and/or expressed at an increased level as compared to a control or a patient that does not have detectable levels of the PVRIG and/or DNAM-1 in the biological sample.
A method for predicting or determining the efficacy of treatment for a cancer patient with an anti-PVRIG treatment antibody, the method comprising:
- (a) measuring the level of PVRIG and/or DNAM-1 expression in a biological sample obtained from a cancer and/or tumor microenvironment and/or peripheral blood in the cancer patient,
- (b) quantitating the measurement of the level of PVRIG and/or DNAM-1 expression in the biological sample, and
- (c) correlating the level of PVRIG and/or DNAM-1 with the efficacy of treatment, wherein PVRIG and/or DNAM-1 is expressed and/or expressed at an increased level as compared to a control or a patient that does not have detectable levels of the PVRIG and/or DNAM-1, is indicative of treatment efficacy for treatment with an anti-PVRIG treatment antibody.
A method for altering the regimen of treatment for a patient with cancer, the method comprising:
- (a) measuring the level of PVRIG and/or DNAM-1 expression in a biological sample obtained from a cancer and/or tumor microenvironment and/or peripheral blood in the cancer patient,
- (b) quantitating the measurement of the level of PVRIG and/or DNAM-1 expression in the biological sample, wherein PVRIG and/or DNAM-1 being expressed and/or being expressed at an increased level as compared to a control or a patient that does not have detectable levels of the PVRIG and/or DNAM-1 is indicative of treatment efficacy,
- (c) correlating the level of PVRIG and/or DNAM-1 expression with the efficacy of treatment, wherein a high level of PVRIG and/or DNAM-1 expression is indicative of altering the treatment regimen for treatment with anti-PVRIG treatment antibody, and
- (d) altering the treatment regimen to include an anti-PVRIG antibody when a moderate or high level of PVRIG and/or DNAM-1 expression is measured.
The method according to 123, wherein the single-cell resolution analysis includes RNAseq, immunohistochemistry (IHC), multiplex immunohistochemistry (mIHC) and/or immunofluorescence (IF), flow cytometry (e.g., FACS) and mass cytometry (e.g., CyTOF), as well as combinations thereof.
The method according to any one of claims 123 to 126, wherein an anti-PVRIG antibody is used for the single-cell resolution analysis and/or immunohistochemistry, and wherein the anti-PVRIG antibody is AB-635 PVRIG Ab (6D8-1 clone).
Dependencies are inferred from the claim text.