Multispecific chimeric receptors

A DNA molecule encoding a chimeric membrane bound protein, said chimeric protein comprising in the N-terminal to C-terminal direction:

• at least two extracellular inducer-responsive clustering domains in tandem to form a multispecific extracellular inducer-responsive clustering domain that binds specifically to at least one inducer molecule which results in the dimerization or oligomerization of said multispecific extracellular domain;
• a transmembrane domain;
• a cytoplasmic domain comprising a Janus kinase;
• and
• a cytoplasmic domain comprising .zeta. or .eta. chain of the T-cell receptor;
• wherein when said membrane bound protein is expressed in a selected host cell under conditions suitable for expression, said membrane bound protein initiates a signal for proliferation and effector function in said host cell on binding to said at least one inducer molecule.

A DNA molecule encoding a chimeric membrane bound protein, said chimeric protein comprising in the N-terminal to C-terminal direction:

• at least two extracellular inducer-responsive clustering domains in tandem to form a multispecific extracellular inducer-responsive clustering domain that binds specifically to at least one inducer molecule which results in the dimerization or oligomerization of said multispecific extracellular domain;
• a transmembrane domain;
• a cytoplasmic domain comprising .zeta. or .eta. chain of the T-cell receptor;
• and
• a cytoplasmic domain comprising a Janus kinase;
• wherein when said membrane bound protein is expressed in a selected host cell under conditions suitable for expression, said membrane bound protein initiates a signal for proliferation and effector function in said host cell on binding to said at least one inducer molecule.

A DNA molecule encoding a hybrid extracellular and intracellular multispecific chimeric receptor protein, said chimeric protein comprising in the N-terminal to C-terminal direction:

• at least two extracellular inducer-responsive clustering domains in tandem to form a multispecific extracellular inducer-responsive clustering domain that binds specifically to at least one inducer molecule which results in the dimerization or oligomerization of said multispecific extracellular domain;
• a transmembrane domain:
• a cytoplasmic domain comprising a Janus kinase;
• and
• an intracellular inducer-responsive clustering domain comprising an immunophilin or a cyclophilin;
• wherein when said chimeric receptor protein is expressed in a selected host cell under conditions suitable for expression, said receptor protein initiates a signal for proliferation in said host cell on binding to said at least one inducer molecule.

A DNA molecule encoding a hybrid multispecific chimeric receptor protein, said protein comprising in the N-terminal to C-terminal direction:

• at least two extracellular inducer-responsive clustering domains in tandem to form a multispecific extracellular inducer-responsive clustering domain that binds specifically to at least one inducer molecule which results in the dimerization or oligomerization of said multispecific extracellular domain;
• a transmembrane domain;
• a cytoplasmic domain comprising a Janus kinase;
• a cytoplasmic domain comprising a .zeta. or .eta. chain of the T-cell receptor;
• and
• an intracellular inducer-responsive clustering domain comprising an immunophilin or a cyclophilin;
• wherein when said hybrid multispecific chimeric receptor is expressed in a selected host cell under conditions suitable for expression, said receptor protein initiates a signal for proliferation and effector function in said host cell on binding to said at least one inducer molecule.

A chimeric protein comprising in the N-terminal to C-terminal direction:

• a multispecific extracellular inducer-responsive clustering domain comprising at least two domains in tandem that bind specifically to at least one inducer-molecule which results in the dimerization or oligomerization of said multispecific extracellular domain;
• a transmembrane domain;
• and
• a cytoplasmic domain comprising a .zeta. or .eta. chain of the T-cell receptor, or a Janus kinase;
• wherein when said chimeric protein is expressed as a membrane bound protein in a selected host cell under conditions suitable for expression, said membrane bound protein initiates a signal in said host cell on binding to said at least one inducer molecule.

A chimeric protein comprising in the N-terminal to C-terminal direction:

• a multispecific extracellular inducer-responsive clustering domain comprising at least two domains in tandem that bind specifically to at least one inducer-molecule which results in the dimerization or oligomerization of said multispecific extracellular domain;
• a transmembrane domain;
• a cytoplasmic domain comprising a Janus kinase;
• and
• a cytoplasmic domain comprising .zeta. or .eta.;
• wherein when said chimeric protein is expressed as a membrane bound protein in a selected host cell under conditions suitable for expression, said membrane bound protein initiates a signal for proliferation and effector function in said host cell on binding to said at least one inducer molecule.

A chimeric protein comprising in the N-terminal to C-terminal direction:

• a multispecific extracellular inducer-responsive clustering domain comprising at least two domains in tandem that bind specifically to at least one inducer-molecule which results in the dimerization or oligomerization of said multispecific extracellular domain;
• a transmembrane domain;
• a cytoplasmic domain comprising .zeta. or .eta. chain of the T-cell receptor;
• and
• a cytoplasmic domain comprising a Janus kinase;
• wherein when said chimeric protein is expressed as a membrane bound protein in a selected host cell under conditions suitable for expression, said membrane bound protein initiates a signal for proliferation and effector function in said host cell on binding to said at least one inducer molecule.

A chimeric hybrid binding protein comprising in the N-terminal to C-terminal direction:

• a multispecific extracellular inducer-responsive clustering domain comprising at least two domains in tandem that bind specifically to at least one inducer molecule which results in the dimerization or oligomerization of said multispecific extracellular domain;
• a transmembrane domain;
• a cytoplasmic domain comprising a Janus kinase;
• and
• an intracellular inducer-responsive clustering domain comprising an immunophilin or a cyclophilin;
• wherein when said chimeric hybrid binding protein is expressed as a protein receptor in a selected host cell under conditions suitable for expression, said protein receptor initiates a signal for proliferation in said host cell on binding to either said inducer molecule or combinations thereof.

A chimeric hybrid binding protein comprising in the N-terminal to C-terminal direction:

• a multispecific extracellular inducer-responsive clustering domain comprising at least two domains in tandem that bind specifically to at least one inducer molecule which results in the dimerization or oligomerization of said multispecific extracellular domain;
• a transmembrane domain;
• a cytoplasmic domain comprising a Janus kinase;
• a cytoplasmic domain comprising .zeta. or .eta. chain of the T-cell receptor;
• and
• an intracellular inducer-responsive clustering domain comprising an immunophilin or a cyclophilin;
• wherein when said chimeric hybrid binding protein is expressed as a protein receptor in a selected host cell under conditions suitable for expression, said protein receptor initiates a signal for proliferation in said host cell on binding to either said inducer molecule or combinations thereof.