Active cxcr4+ immune cells and methods for their production and use

Abstract

Provided herein are active CXCR4+ CD8; T cells, active CXCR4+ type-1 CD4+ T cells and active CXCR4+ NK cells and populations of those cells, methods for making active CXCR4+ T cells and NK cells and populations of those cells, and methods for using active CXCR4+ T cells and NK cells and populations of those cells for the treatment of cancer, precartcerous conditions and chronic infections.

1 - 12 . (canceled) 
     
     
         13 . A method of treating a cancer in a subject comprising administering to the subject a therapeutically effective amount of one or more of a type-1 polarized active CXCR4 + CD8 +  T cell or cell population, an a type-1 polarized active CXCR4 + Th1-type-CD4 +  T cell or cell population, or a type-1 polarized active CXCR4 + NK cell or cell population having been exposed to a hypoxic condition and comprising an increased surface expression of a CXCR4 as compared to a control CD8 +  T cell or cell population, a control CD4 +  T cell or cell population, or a control NK cell or cell population, respectively. 
     
     
         14 . The method of  claim 13 , wherein the cancer is a solid tumor or a hematologic cancer containing involvement of a solid tissue selected from bone marrow and lymphoid tissue. 
     
     
         15 . The method of  claim 13 , wherein the increased CXCR4 surface expression is at least 5% higher than the control cell or cell population. 
     
     
         16 . The method of  claim 13 , wherein the type-1 polarized active CXCR4 + CD8 + T cell or cell population, type-1 polarized active CXCR4 + Th1-type-CD4 +  T cell or cell population or type-1 polarized active CXCR4 + NK cell or cell population are non-recombinant. 
     
     
         17 . The method of  claim 13 , wherein the type-1 polarized active CXCR4 + CD8 + T cell or cell population [[and]] or the type-1 polarized active CXCR4 + NK cell or cell population are cytotoxic. 
     
     
         18 . A method of treating a precancerous condition or chronic infection in a subject comprising administering to the subject a pharmaceutically effective amount of one or more of a type-1 polarized active CXCR4 + CD8 +  T cell or cell population, a type-1 polarized active CXCR4 + Th1-type-CD4 +  T cell or cell population, or a type-1 polarized active CXCR4 + NK cell or cell population having been exposed to a hypoxic condition comprising an increased surface expression of a CXCR4 as compared to a control CD8 +  T cell or cell population, a control CD4 +  T cell or cell population, or a control NK cell or cell population, respectively. 
     
     
         19 . The method of  claim 18 , wherein the increased CXCR4 surface expression is at least 5% higher than the control cell or cell population. 
     
     
         20 . The method of  claim 18 , wherein the type-1 polarized active CXCR4 + CD8 +  T cell, CXCR4 + CD4 +  T cell or CXCR4 + NK cell are non-recombinant. 
     
     
         21 . The method of  claim 18 , wherein the type-1 polarized active CXCR4 + CD8 +  T cell or cell population or the type-1 polarized active CXCR4 + NK cell or cell population are cytotoxic. 
     
     
         22 - 26 . (canceled) 
     
     
         27 . The method of  claim 13 , wherein the type-1 polarized active CXCR4+CD8+ T cell or cell population or the type-1 polarized active CXCR4+Th1-type-CD4+ T cell or cell population is recombinant. 
     
     
         28 . The method of  claim 13 , wherein the type-1 polarized active CXCR4+CD8+ T cell or cell population or the type-1 polarized active CXCR4+Th1-type-CD4+ T cell or cell population comprises a chimeric antigen receptor. 
     
     
         29 . The method of  claim 13 , wherein the type-1 polarized active CXCR4+CD8+ T cell or cell population or the type-1 polarized active CXCR4+Th1-type-CD4+ T cell or cell population comprises a recombinant T cell antigen receptor.