ACTIVATED DUAL SPECIFICITY LYMPHOCYTES AND THEIR METHODS OF USE
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.