Agents and methods for predicting response to therapy

A method for determining increased likelihood of sensitivity of a cancer cell to a cytotoxic therapy or immunotherapy, wherein the increased likelihood of sensitivity is relative to a response to the therapy of a control cancer cell, and wherein the immunotherapy is a PD-1 directed immunotherapy or a PD-L1 directed immunotherapy, the method comprising detecting the presence of PD-L1-K263Me in the cancer cell, to thereby determine that the cancer cell has increased likelihood of sensitivity to the therapy.

A method for predicting a likelihood of response of a cancer cell to a cytotoxic therapy or immunotherapy, wherein the likelihood of response to the therapy is relative to a response to the therapy of a control cancer cell, and wherein the immunotherapy is a PD-1 directed immunotherapy or a PD-L1 directed immunotherapy, the method comprising:

• measuring the level of PD-L1-K263Ac in the cancer cell, measuring the level of PD-L1-K263Me in the cancer cell;
• comparing the level of PD-L1-K263Ac and PD-L1-K263Me in the cancer cell;
• and predicting the response of the cancer cell to the therapy based on a comparison of the level of PD-L1-K263 Ac and the level of PD-L1-K263Me, wherein a higher level of PD-L1-K263Ac than PD-L1-K263Me in the cancer cell indicates that the cancer cell has increased likelihood of resistance to the therapy and wherein a higher level of PD-L1-K263Me than PD-L1-K263Ac in the cancer cell indicates that the cancer cell has increased likelihood of sensitivity to the therapy.

A method for stratifying a cancer patient as a likely responder or non-responder to a cytotoxic therapy or immunotherapy, wherein the immunotherapy is a PD-1 directed immunotherapy or a PD-L1 directed immunotherapy, the method comprising detecting in a sample taken from the patient a cancer cell that comprises a post-translational modification in the nuclear localization sequence of PD-L1, wherein the post-translational modification is PD-L1-K263Ac or PD-L1-K263Me, wherein if PD-L1-K263Ac is detected in the cancer cell, the patient is stratified as a likely non-responder to the therapy, and wherein if PD-L1-K263Me is detected in the cancer cell, the patient is stratified as a likely responder to the therapy.

A method for stratifying a cancer patient as a likely responder or non-responder to a cytotoxic therapy or immunotherapy, wherein the immunotherapy is a PD-1 directed immunotherapy or a PD-L1 directed immunotherapy, the method comprising:

• contacting a sample comprising a cancer cell taken from the patient with a first antigen-binding molecule that binds specifically to PD-L1-K263Ac and a second antigen-binding molecule that binds specifically to PD-L1-K263Me;
• measuring in the sample the level of a first complex that comprises the first antigen-binding molecule and PD-L1-K263Ac, and the level of a second complex that comprises the second antigen-binding molecule and PD-L1-K263Me;
• and stratifying the patient as a likely responder or non-responder based on a comparison of the level of the first complex and the level of the second complex, wherein the patient is stratified as a likely non-responder if the level of the first complex is higher than the second complex in the sample and wherein the patient is stratified as a likely responder if the level of the second complex is higher than the first complex in the sample.

A method for managing treatment of a cancer patient with a cytotoxic therapy or immunotherapy, wherein the immunotherapy is a PD-1 directed immunotherapy or a PD-L1 directed immunotherapy, the method comprising selecting a cancer patient for treatment with the therapy on the basis that the patient is a likely responder to the therapy, or selecting a cancer patient for not treating with the therapy on the basis that the patient is a likely non-responder to the therapy and treating or not treating the patient with the therapy based on the selection, wherein the selection is based on a stratification method that comprises detecting in a sample taken from the patient a cancer cell that comprises a post-translational modification in the nuclear localization sequence of PD-L1, to thereby stratify the patient as a likely responder or non-responder to the therapy, wherein if PD-L1-K263Me is detected in the cancer cell, the patient is stratified as a likely responder to the therapy, and wherein if PD-L1-K263 Ac is detected in the cancer cell, the patient is stratified as a likely non-responder to the therapy.