Activated dual specificity lymphocytes and their methods of use

Abstract

The present invention relates to preventive, therapeutic, and diagnostic compositions and methods employing lymphocytes having T-cell receptors and chimeric receptors. In particular, the invention relates to pre-selected dual-specificity lymphocytes having endogenous T-cell receptors and chimeric T-cell receptors that recognize a strong antigen and tumor associated antigens where the pre-selected population of adoptively transferred lymphocytes is activated by in vivo immunization, thereby increasing the effectiveness of adoptive immunotherapy.

1 . A composition comprising a T lymphocyte having a chimeric receptor or T-cell receptor reactive with a tumor antigen and an endogenous T-cell receptor reactive with a cell that is allogeneic to the T lymphocyte. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The composition of  claim 1  wherein the tumor antigen is an ovarian tumor antigen. 
     
     
         5 . The composition of  claim 1  wherein the tumor antigen is a melanoma antigen. 
     
     
         6 . (canceled) 
     
     
         7 . The composition of  claim 1  wherein the chimeric receptor is a single chain Fv receptor. 
     
     
         8 . The composition of  claim 1  wherein the allogeneic cell is an allogeneic peripheral blood cell. 
     
     
         9 . (canceled) 
     
     
         10 . The composition of  claim 1  wherein the chimeric receptor is Mov-γ. 
     
     
         11 . (canceled) 
     
     
         12 . A lymphocyte comprising a T-cell receptor reactive with an allogeneic cell and a chimeric receptor reactive with a tumor antigen, wherein the lymphocyte is activated in vivo with the allogeneic cell. 
     
     
         13 .- 14 . (canceled) 
     
     
         15 . The lymphocyte according to  claim 12  wherein the allogeneic cell is a peripheral blood cell. 
     
     
         16 .- 39 . (canceled) 
     
     
         40 . A pharmaceutical composition comprising:
 a T lymphocyte comprising a chimeric receptor reactive with a tumor antigen and an endogenous T-cell receptor reactive with a cell that is allogeneic to the T lymphocyte; and   a pharmaceutically acceptable carrier.   
     
     
         41 .- 43 . (canceled) 
     
     
         44 . The composition of  claim 4 , wherein the ovarian tumor antigen is folate binding protein (FBP). 
     
     
         45 . The composition of  claim 1 , wherein the T lymphocyte is a human T lymphocyte. 
     
     
         46 . The lymphocyte of  claim 12 , wherein the lymphocyte is a human lymphocyte. 
     
     
         47 . The lymphocyte of  claim 12 , wherein the tumor antigen is an ovarian tumor antigen. 
     
     
         48 . The lymphocyte of  claim 47 , wherein the ovarian tumor antigen is FBP. 
     
     
         49 . The lymphocyte of  claim 12 , wherein the chimeric receptor is Mov-γ. 
     
     
         50 . A pharmaceutical composition comprising the lymphocyte of  claim 12  and a pharmaceutically acceptable carrier. 
     
     
         51 . A composition comprising the lymphocytes prepared by
 selecting for lymphocytes reactive with an allogeneic cell ex vivo; and   transducing the lymphocytes with a chimeric receptor gene, said gene encoding a receptor which is reactive with a tumor antigen.   
     
     
         52 . A composition comprising a population of T lymphocytes comprising
 (a) a chimeric receptor or T cell receptor that is reactive with a tumor antigen, and   (b) a T-cell receptor that is reactive with an allogeneic cell,   wherein the population of T lymphocytes has been exposed to a cell that is allogeneic to an individual or subpopulation of T lymphocytes of the population under conditions which expand and activate the individual or subpopulation of T lymphocytes.   
     
     
         53 . The composition of  claim 52 , wherein the tumor antigen is an ovarian tumor antigen. 
     
     
         54 . The composition of  claim 53 , wherein the ovarian tumor antigen is folate binding protein (FBP). 
     
     
         55 . The composition of  claim 52 , wherein the cell is a peripheral blood mononuclear cell, splenocyte, a dendritic cell, or a B cell. 
     
     
         56 . The composition of  claim 52 , wherein the T lymphocyte is a human T lymphocyte. 
     
     
         57 . The composition of  claim 52 , wherein the population further comprises the cell that is allogeneic to the T lymphocytes. 
     
     
         58 . The composition of  claim 51 , further comprising the cell that is allogeneic to the lymphocytes.