Dendritic cells having enhanced yo t-cell activating and/or proliferating activity and methods of preparation or use thereof

Abstract

A therapeutic method, which includes administering dendritic cells pulsed in vitro with a bisphosphonate-based bone metabolism improving drug, is provided. The dendritic cells may be capable of efficiently activating and/or proliferating γδ T-cells in vivo and/or in vitro. This can permit for easy proliferation of γδ T-cells without burdening a patient, leading to practical applications of immune cell therapies that utilize γδ T-cells.

1 . A therapeutic method wherein cultured, isolated dendritic cells which have been pulsed with a bisphosphonate-based bone metabolism improving drug in vitro, are administered to a patient in an amount effective for treating a cancer and/or an infectious disease. 
     
     
         2 . The therapeutic method of  claim 1 , wherein said cultured, isolated dendritie cells have enhanced functional activity for activating and/or proliferating γδ T-cells in culture in relation to cultured, isolated dendritic cells which have not been exposed to a bisphosphonate-based bone metabolism improving drug. 
     
     
         3 . The therapeutic method of  claim 1 , wherein said cultured, isolated dendritic cells are immature dendritic cells. 
     
     
         4 . The therapeutic method of  claim 1 , wherein said cultured, isolated dendritic cells are a mixture of immature and mature dendrite cells. 
     
     
         5 . The therapeutic method of  claim 1 , wherein said bisphosphonate-based bone metabolism improving drug is selected from the group consisting pamidronic acid, alendronic acid, zoledronic acid, risedronic acid, ibandronic acid, incadronic acid, etidronic acid, their salts their hydrates and combinations thereof. 
     
     
         6 . The therapeutic method of  claim 1 , wherein said cultured, isolated dendritic cells are produced by a process comprising:
 a) differentiating precursor cells in vitro, wherein the precursor cells are selected from the group consisting (i) isolated CD14 positive cells; (ii) isolated peripheral blood mononuclear cells; (iii) isolated CD34 positive hematopoietic stem cells; and (iv) a mixture thereof, to provide isolated, cultured dendritic cells; and   b) pulsing the cultured isolated dendritic cells with said bisphosphonate-based bone metabolism improving drug.   
     
     
         7 . The therapeutic method of  claim 6  wherein said precursor cells are derived from said patient. 
     
     
         8 . The therapeutic method of  claim 2  wherein said cultured, isolated dendritic cells comprise immature dendritic cells. 
     
     
         9 . The method of  claim 8 , wherein the bisphosphonate-based bone metabolism improving drug is pamidronic acid, a salt thereof, a hydrate thereof, or a mixture thereof. 
     
     
         10 . The method of  claim 8 , wherein the bisphosphonate-based bone metabolism improving drug is alendronic acid, a salt thereof, a hydrate thereof, or a mixture thereof. 
     
     
         11 . The method of  claim 8 , wherein the bisphosphonate-based bone metabolism improving drug is zoledronic acid, a salt thereof, a hydrate thereof, or a mixture thereof. 
     
     
         12 . The therapeutic method of  claim 2  wherein said cultured, isolated dendritic cells are administered to the patient in an amount effective for treating a cancer. 
     
     
         13 . The therapeutic method of  claim 2  wherein said cultured, isolated dendritic cells are administered to the patient in an amount effective for treating an infectious disease. 
     
     
         14 . The therapeutic method of  claim 2  wherein said infectious disease is a bacterial infection.