Endowing lymphocytes with antibody specificity
First Claim
1. A mononuclear T-killer cell which expresses a chimeric receptor which permits said cell to selectively kill target cells bearing a predefined target antigen in a non-MHC restricted manner, said cell containing recombinant DNA encoding said chimeric receptor, said DNA comprising:
- a. DNA coding for the two chains of the constant region of a T-cell receptor (TcR), said two chains being the α and
β
chains or the γ and
δ
chains, andb. DNA coding for the variable regions of the heavy and light chains of an antibody specific for the predefined target antigen, such that, when expressed, one of said heavy and light chains of said antibodies is attached to one of said two chains of said T-cell constant region and the other of said heavy and light chains of said antibodies is attached to the other of said two chains of said T-cell constant regions.
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Accused Products
Abstract
There are produced recombinant gene pairs which endow mononuclear cells, mainly various lymphocyte type cells, with antibody-type specificity. In specific gene pairs the rearranged gene pairs code for a binding site of an antibody molecule from the same species, of the T-cell receptor gene, or another species. Gene pairs of the invention code, for example, for antibodies specific towards tumor-specific antigens, viral antigens, modified self antigens, bacterial or fungal antigens, autoimmune type disease antigens and the like. The invention further relates to expression vectors for the effective transfection of such cell types comprising such a recombinant gene pair, to methods for producing same and to pharmaceutical compositions comprising as active ingredient an effective quantity of lymphocytes transfected with such gene pairs.
134 Citations
33 Claims
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1. A mononuclear T-killer cell which expresses a chimeric receptor which permits said cell to selectively kill target cells bearing a predefined target antigen in a non-MHC restricted manner, said cell containing recombinant DNA encoding said chimeric receptor, said DNA comprising:
-
a. DNA coding for the two chains of the constant region of a T-cell receptor (TcR), said two chains being the α and
β
chains or the γ and
δ
chains, andb. DNA coding for the variable regions of the heavy and light chains of an antibody specific for the predefined target antigen, such that, when expressed, one of said heavy and light chains of said antibodies is attached to one of said two chains of said T-cell constant region and the other of said heavy and light chains of said antibodies is attached to the other of said two chains of said T-cell constant regions. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11)
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12. A mononuclear lymphocyte cell which expresses a chimeric receptor which permits said cell to direct its cellular immune response toward a predefined target antigen in a non-MHC restricted manner, said cell containing recombinant DNA encoding said chimeric receptor, said DNA comprising:
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a. DNA coding for an α
, β
, γ
or δ
chain of the constant region of a T-cell receptor (TcR), andb. DNA coding for the VH region of an antibody specific for the predefined target antigen, wherein said antibody is specific towards a tumor specific antigen, a tumor associated antigen, a viral antigen, or an autoimmune disease type antigen. - View Dependent Claims (13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
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23. A mononuclear lymphocyte cell which expresses a chimeric receptor which permits said cell to direct its cellular immune response toward a predefined target antigen in a non-MHC restricted manner, said cell containing recombinant DNA encoding said chimeric receptor, said DNA comprising:
-
a. DNA coding for the two chains of the constant region of a T-cell receptor (TcR), said two chains being the α and
β
chains or the γ and
δ
chains, andb. DNA coding for the variable regions of the heavy and light chains of an antibody specific for the predefined target antigen, such that, when expressed, one of said heavy and light chains of said antibody is attached to one of said two chains of said T-cell constant region and the other of said heavy and light chains of said antibody is attached to the other of said two chains of said T-cell constant regions, wherein said heavy and light chains are from an antibody specific towards tumor specific antigens, tumor associated antigens, viral antigens, or autoimmune disease type antigens.
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24. A human mononuclear lymphocyte cell which expresses a chimeric receptor which permits said cell to direct its cellular immune response toward a predefined target antigen in a non-MHC restricted manner, said cell containing recombinant DNA encoding said chimeric receptor, said DNA consisting essentially of:
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a. DNA coding for an α
, β
, γ
or δ
chain of the constant region of a T-cell receptor (TcR), andb. DNA coding for the VH region of an antibody specific for the predefined target antigen. - View Dependent Claims (25, 26)
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27. A human mononuclear lymphocyte cell which expresses a chimeric receptor which permits said cell to direct its cellular immune response toward a predefined target antigen in a non-MHC restricted manner, said cell containing recombinant DNA encoding said chimeric receptor, said DNA comprising:
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a. DNA coding for the two chains of the constant region of a T-cell receptor (TcR), said two chains being the α and
β
chains or the γ and
δ
chains, andb. DNA coding for the variable regions of the heavy and light chains of an antibody specific for the predefined target antigen, such that, when expressed, one of said heavy and light chains of said antibody is attached to one of said two chains of said T-cell constant region and the other of said heavy and light chains of said antibody is attached to the other of said two chains of said T-cell constant regions.
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28. A process of directing the immune response of a patient toward a predefined target antigen, comprising the steps of:
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(1) transfecting mononuclear lymphocyte cells with a recombinant DNA comprising (a) DNA coding for an α
, β
, γ
or δ
chain of the constant region of a T-cell receptor (TcR), and(b) DNA coding for the VH region of an antibody specific for the predefined target antigen, and (2) inoculating the patient with the transfected lymphocyte cells. - View Dependent Claims (29, 30, 31, 32)
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33. A process for producing a vector containing a DNA sequence coding for an antibody variable region and a DNA sequence coding for the constant region of a T-cell receptor (TcR), comprising:
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preparing a TcR expression cassette containing regulatory regions and the DNA encoding the constant region of a TcR; amplifying by polymerase chain reaction an antibody variable region of known or unknown sequence using primers composed of consensus sequences of JH or JC for the 3'"'"' end and poly(dG) tail for the 5'"'"' end; and cloning the amplified antibody variable regions directly into said TcR expression cassette.
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Specification