Method for treating epstein-barr virus - positive cancer with immunotherapy

Abstract

A method for predicting whether a patient will be a long-term survivor on treatment of a disease by adoptive cell transfer (ACT), is disclosed comprising: (i) analysing a blood-derived sample obtained from the patient for one or more prognostic markers of long-term survival on treatment of a disease by ACT, and; (ii) based on the analysis of step (i), predicting whether the patient will be a long-term survivor on treatment of the disease by ACT. Also disclosed are methods for treating a patient by ACT, methods for selecting a patient for treatment by ACT, and methods for selecting a patient for treatment of a disease by ACT.

1 - 20 . (canceled) 
     
     
         21 . A method of treating an Epstein-Barr Virus (EBV)-positive cancer in a patient by adoptive cell transfer (ACT) of EBV-specific CTLs, the method comprising:
 (i) analysing a correlate of myeloid-derived suppressor cell (MDSC) number or activity in a blood-derived sample obtained from the patient;   (ii) based on step (i), predicting whether the patient will be a long-term survivor on treatment of the EBV-positive cancer by ACT of EBV-specific CTLs; and   (iii) administering one or more doses of EBV-specific CTLs to a patient predicted in step (ii) to be a long-term survivor on treatment of the EBV-positive cancer by ACT of EBV-specific CTLs.   
     
     
         22 . The method according to  claim 21 , wherein the correlate of MDSC number or activity is selected from: the percentage of MDSCs amongst peripheral blood mononuclear cells (PBMCs), the percentage of monocytes amongst PBMCs, and the percentage of monocytes amongst leukocytes. 
     
     
         23 . The method according to  claim 21 , wherein analysing a correlate of MDSC number or activity in a blood-derived sample obtained from the patient comprises determining the percentage of MDSCs amongst peripheral blood mononuclear cells (PBMCs), the percentage of monocytes amongst PBMCs, or the percentage of monocytes amongst leukocytes in a blood-derived sample obtained from the patient, and comparing the determined percentage to a reference value which is indicative of long-term survival or non-survival of a patient on treatment of the EBV-positive cancer by ACT of EBV-specific CTLs. 
     
     
         24 . The method according to  claim 21 , wherein the blood derived-sample is obtained from the patient after completion of a course of chemotherapy. 
     
     
         25 . The method according to  claim 24 , wherein the chemotherapy comprises treatment with gemcitabine and/or carboplatin. 
     
     
         26 . The method according to  claim 21 , wherein the EBV-positive cancer is selected from: EBV-positive nasopharyngeal carcinoma (NPC), EBV-positive liver cancer, EBV-positive lung cancer, and EBV-positive gastric cancer. 
     
     
         27 . A method of treating an Epstein-Barr Virus (EBV)-positive cancer in a patient by adoptive cell transfer (ACT) of EBV-specific CTLs, the method comprising:
 (i) analysing a correlate of myeloid-derived suppressor cell (MDSC) number or activity in a blood-derived sample obtained from the patient;   (ii) based on step (i), predicting whether the patient will be a long-term survivor on treatment of the EBV-positive cancer by ACT of EBV-specific CTLs;   (iii) selecting a patient predicted to be a long-term survivor on treatment of the EBV-positive cancer by ACT of EBV-specific CTLs for treatment by ACT of EBV-specific CTLs; and   (iv) administering one or more doses of EBV-specific CTLs to the patient selected in step (iii).   
     
     
         28 . The method according to  claim 27 , wherein the correlate of MDSC number or activity is selected from: the percentage of MDSCs amongst peripheral blood mononuclear cells (PBMCs), the percentage of monocytes amongst PBMCs, and the percentage of monocytes amongst leukocytes. 
     
     
         29 . The method according to  claim 27 , wherein analysing a correlate of MDSC number or activity in a blood-derived sample obtained from the patient comprises determining the percentage of MDSCs amongst peripheral blood mononuclear cells (PBMCs), the percentage of monocytes amongst PBMCs, or the percentage of monocytes amongst leukocytes in a blood-derived sample obtained from the patient, and comparing the determined percentage to a reference value which is indicative of long-term survival or non-survival of a patient on treatment of the EBV-positive cancer by ACT of EBV-specific CTLs. 
     
     
         30 . The method according to  claim 27 , wherein the blood derived-sample is obtained from the patient after completion of a course of chemotherapy. 
     
     
         31 . The method according to  claim 30 , wherein the chemotherapy comprises treatment with gemcitabine and/or carboplatin. 
     
     
         32 . The method according to  claim 27 , wherein the EBV-positive cancer is selected from: EBV-positive nasopharyngeal carcinoma (NPC), EBV-positive liver cancer, EBV-positive lung cancer, and EBV-positive gastric cancer. 
     
     
         33 . A method of treating an Epstein-Barr Virus (EBV)-positive cancer in a patient by adoptive cell transfer (ACT) of EBV-specific CTLs, the method comprising:
 (i) administering a course of chemotherapy to the patient;   (ii) analysing a correlate of myeloid-derived suppressor cell (MDSC) number or activity in a blood-derived sample obtained from the patient;   (iii) based on step (ii), predicting whether the patient will be a long-term survivor on treatment of the EBV-positive cancer by ACT of EBV-specific CTLs;   (iv) selecting a patient predicted to be a long-term survivor on treatment of the EBV-positive cancer by ACT of EBV-specific CTLs for treatment by ACT of EBV-specific CTLs; and   (v) administering one or more doses of EBV-specific CTLs to the patient selected in step (iv).   
     
     
         34 . The method according to  claim 33 , wherein the correlate of MDSC number or activity is selected from: the percentage of MDSCs amongst peripheral blood mononuclear cells (PBMCs), the percentage of monocytes amongst PBMCs, and the percentage of monocytes amongst leukocytes. 
     
     
         35 . The method according to  claim 33 , wherein analysing a correlate of MDSC number or activity in a blood-derived sample obtained from the patient comprises determining the percentage of MDSCs amongst peripheral blood mononuclear cells (PBMCs), the percentage of monocytes amongst PBMCs, or the percentage of monocytes amongst leukocytes in a blood-derived sample obtained from the patient, and comparing the determined percentage to a reference value which is indicative of long-term survival or non-survival of a patient on treatment of the EBV-positive cancer by ACT of EBV-specific CTLs. 
     
     
         36 . The method according to  claim 33 , wherein the chemotherapy comprises treatment with gemcitabine and/or carboplatin. 
     
     
         37 . The method according to  claim 33 , wherein the EBV-positive cancer is selected from: EBV-positive nasopharyngeal carcinoma (NPC), EBV-positive liver cancer, EBV-positive lung cancer, and EBV-positive gastric cancer.