Preparation and application of anti-tumor bifunctional fusion proteins

An isolated nucleic acid comprising a nucleotide sequence encoding a chimeric protein comprising a Flt3 ligand, or a biologically active fragment thereof, and a proteinaceous or peptidyl tumoricidal agent other than TRAIL.

A pharmaceutical composition comprising an effective amount of a chimeric protein comprising a Flt3 ligand, or a biologically active fragment thereof, and a proteinaceous or peptidyl tumoricidal agent, and a pharmaceutically acceptable carrier or excipient.

A kit comprising an effective amount of a chimeric protein comprising a Flt3 ligand, or a biologically active fragment thereof, and a proteinaceous or peptidyl tumoricidal agent, and instructions for administering said chimeric protein.

A method for treating cancer in a mammal so affected, which method comprises administering to the mammal an effective amount of an isolated chimeric protein comprising a Flt3 ligand, or a biologically active fragment thereof, and a proteinacuous or peptidyl tumoricidal agent, wherein the cancer expresses a target for the proteinaceous or peptidyl tumoricidal agent.

A combination, which combination comprises:

• a) an effective amount of a chimeric protein comprising a Flt3 ligand, or a biologically active fragment thereof, and a proteinaceous or peptidyl tumoricidal agent;
• and
• b) an effective amount of an anti-neoplastic agent.

A method for inducing caspase-3 mediated apoptosis in a cell, which method comprises contacting the cell with an effective amount of an isolated chimeric protein comprising an isolated Flt3 ligand, or a biologically active fragment thereof, and a proteinaceous or peptidyl tumoricidal agent, wherein the cell expresses a target for the proteinaceous or peptidyl tumoricidal agent.

A vaccine comprising an effective amount of a chimeric protein comprising a Flt3 ligand, or a biologically active fragment thereof, and a proteinaceous or peptidyl tumoricidal agent and an immune response potentiator.

A method for producing a tumor-specific lymphocyte, which method comprises administering to a mammal an effective amount of an isolated chimeric protein comprising a Flt3 ligand, or a biologically active fragment thereof, and a proteinaceous or peptidyl tumoricidal agent to generate a tumor-specific lymphocyte, and recovering said generated tumor-specific lymphocyte from said mammal.

An isolated chimeric protein, which chimeric protein comprises a Flt3 ligand, or a biologically active fragment thereof, and a proteinaceous or peptidyl targeting agent which binds to a receptor expressed on tumor cells other than the Fc receptor.

A pharmaceutical composition comprising an effective amount of a chimeric protein comprising a Flt3 ligand, or a biologically active fragment thereof, and a targeting agent which binds to a receptor expressed on tumor cells other than the Fc receptor, and a pharmaceutically acceptable carrier or excipient.

A kit comprising an effective amount of a chimeric protein comprising a Flt3 ligand, or a biologically active fragment thereof, and a targeting agent which binds to a receptor expressed on tumor cells other than the Fc receptor, and instructions for administering said chimeric protein.

A method for treating cancer in a mammal so affected, which method comprises administering to the mammal an effective amount of an isolated chimeric protein comprising a Flt3 ligand, or a biologically active fragment thereof, and a targeting agent which binds to a receptor expressed on tumor cells other than the Fc receptor, wherein the cancer expresses a receptor for the targeting agent.

A combination, which combination comprises:

• a) an effective amount of a chimeric protein comprising a Flt3 ligand, or a biologically active fragment thereof, and a targeting agent which binds to a receptor expressed on tumor cells other than the Fc receptor;
• and
• b) an effective amount of an anti-neoplastic agent.

A method for inducing caspase-3 mediated apoptosis in a cell, which method comprises contacting the cell with an effective amount of an isolated chimeric protein comprising an isolated Flt3 ligand, or a biologically active fragment thereof, and a targeting agent which binds to a receptor expressed on tumor cells other than the Fc receptor, wherein the cell expresses a receptor for the targeting agent.

A vaccine comprising an effective amount of a chimeric protein comprising a Flt3 ligand, or a biologically active fragment thereof, and and a targeting agent which binds to a receptor expressed on tumor cells other than the Fc receptor, and an immune response potentiator.

A method for producing a tumor-specific lymphocyte, which method comprises administering to a mammal an effective amount of an isolated chimeric protein comprising a Flt3 ligand, or a biologically active fragment thereof, and a targeting agent which binds to a receptor expressed on tumor cells other than the Fc receptor, to generate a tumor-specific lymphocyte, and recovering said generated tumor-specific lymphocyte from said mammal.