Compositions and methods for enhanced tumor cell immunity in vivo
The invention provides a method of preventing or reducing the severity of a cancer in a subject by stimulating the subject's immune response against the cancer. The invention provides, for example, a method of stimulating an immune response in a subject by administering to the subject tumor cells that are substantially similar to the subject's cancer cells and that are genetically modified to reduce or inhibit the expression of one or more immunosuppressive agents. The invention also provides a method of preventing or reducing the severity of cancer in a subject by stimulating the subject's immune response against the cancer by administering to the subject tumor cells that are substantially similar to the subject's cancer cells and that are genetically modified to prevent the expression of an immunosuppressive agents and, in combination with the genetically modified tumor cells, an immunostimulatory agent. The invention further provides compositions useful for practicing the claimed methods.
1. A method of stimulating an immune response against a cancer, comprising administering to a subject an effective amount of tumor cells that are substantially similar to the subject's cancer cells and that are genetically modified to provide an inhibitor of the expression of at least one immunosuppressive agent, wherein said inhibitor is an antisense molecule to the sequence encoding the immunosuppressive agent,
wherein said tumor cells are the same histologic type as the subject's cancer cells and express at least one antigen that is the same as an antigen expressed by the subject's cancer cells wherein said immunosuppressive agent is TGFβ, fibronectin, tenascin, p15E or lymphocyte blastogenesis inhibitory factor.
2. The method of claim 1 , wherein said tumor cells are derived from said subject.
3. The method of claim 1 , wherein said tumor cells are donor tumor cells.
4. The method of claim 1 , wherein said tumor cells are carcinoma cells, glioma cells, sarcoma cells, lymphoma cells, melanoma cells or leukemia cells.
5. The method of claim 1 , further comprising administering an immunostimulatory agent to said subject.
6. The said method claim 5 , wherein said immunostimulatory agent is a cytokine.
7. The method of claim 6 , wherein said cytokine is interleukin-1, interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-6, interleukin-7, interleukin-12, interleukin-15, gamma-interferon, tumor necrosis factor, granulocyte colony stimulating factor or granulocyte-macrophage colony stimulating factor.
8. The method of claim 6 , wherein said cytokine is interleukin-2.
9. The method of claim 5 , wherein immunostimulatory agent is cytokine-expressing cells.