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US 2003/0157113 A1Published application
Compositions and methods for treatment of neoplastic disease
OwnerDavid S. Termaninventor
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OwnerDavid S. Termaninventor
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The present invention comprises compositions and methods for treating a tumor or neoplastic disease in a host, The methods employ conjugates comprising superantigen polypeptides, nucleic acids with other structures that preferentially bind to tumor cells and are capable of inducing apoptosis. Also provided are superantigen-glycolipid conjugates and vesicles that are loaded onto antigen presenting cells to activate both T cells and NKT cells. Cell-based vaccines comprise tumor cells engineered to express a superantigen along with glycolipids products which, when expressed, render the cells capable of eliciting an effective anti-tumor immune response in a mammal into which these cells are introduced. Included among these compositions are tumor cells, hybrid cells of tumor cells and accessory cells, preferably dendritic cells. Also provided are tumoricidal T cells and NKT cells devoid of inhibitory receptors or inhibitory signaling motifs which are hyperresponsive to the the above compositions and lipid-based tumor associated antigens that can be administered for adoptive immunotherapy of cancer and infectious diseases.
A receptor in a mammalian cell useful in the treatment of cancer which inhibits cellular activation by receptors specific for lipid-based tumor associatiated antigens.
2 The receptor of claim 1 wherein the lipid antigen is a bacterial, fungal, protozoal or mycobacterial antigen.
A receptor in a mammalian cell wherein said receptor inhibits cellular activation by receptors specific for lipid-based infectious disease associated antigens derived from bacteria, fungi, mycobacterium, parasite, virus, eukaryote or prokaryote antigens in the context of MHC or CD1.
A mammalian cell useful in the treatment of cancer wherein the inhibitory receptor for lipid-based tumor associated antigens is deleted or functionally deactivated.
A mammalian cell useful in the treatment of cancer wherein inhibitory receptor tyrosine-based inhibitory motifs of the inhibitory receptor for lipid-based tumor associated antigens are deleted or functionally deactivated.
A mammalian cell useful in the treatment of cancer wherein the the inhibitory receptor for superantigens associated with self antigens are functionally deleted.
A mammalian cell useful in the treatment of cancer wherein the inhibitory receptor for tumor associated lipid antigens and superantigens are deleted or functionally deactivated.
The lipid antigens derived from bacteria, mycobacteria, fungi and protozoa marine invertebrates of claim 2 wherein said lipid antigens are selected from the group consisting of glycosylceramides, glyco lipids, proteolipids, glyco sphingo lipids, gangliosides and sphingolipids with inositolphosphate-containing head groups, phytoglycolipids, mycoglycolipids, lipoarabinan and mycolic acid.
12 The sphingolipid antigens of claim 11 wherein the sphingolipid contains inositolphosphate-containing head groups with the general structure of ceramide-P-myoinositol-X with X referring to polar substituents consisting of ceramide-p-inositol-mannose, inositol-1-P-(6)mannose(a1,2inositol-1P-(1)ceramide, (inositol-P)2-ceramide, inositol-P-inositol-P-ceramide, inositol-P-inositol-P-ceramide.
A mammalian cell useful in the treatment of cancer wherein the inhibitory receptor for glycan-based tumor associated antigens is deleted or functionally deactivated.
A mammalian cell useful in the treatment of cancer wherein the the inhibitory receptor for superantigen-associated self antigens are functionally deleted or inactivated.
A mammalian cell useful in the treatment of cancer wherein the inhibitory receptors and/or immune receptor tyrosine based inhibitory motifs which inhibits cellular activation by receptors specific for lipid-based tumor associated antigens and superantigens are deleted or functionally deactivated.
A mammalian cell in which the inhibitory receptor for lipid-based infectious disease associated antigens and/or immune receptor tyrosine based inhibitory motifs which inhibits cellular activation by receptors specific for lipid-based infectious disease associated antigens derived from bacteria, fungi, mycobacteria, parasite, virus, eukaryote or prokaryote antigens are deleted or functionally deactivated.
24 A method of treating cancer in a mammal, said method comprising inactivating or deleting inhibitory receptors or immune receptor tyrosine based inhibitory motifs in immunocytes which inhibit activating receptors specific for lipid-based tumor associated lipid antigens or superantigens.
A method of inactivation or deletion of receptors or ITIMs in immunocytes which inhibit cell activating receptors specific for lipid-based tumor associated antigens and superantigens comprising inactivation or deletion of nucleic acids encoding ITIMs.
A method for producing a tumoricidal immunocyte population in vivo said method comprising allowing a tumor associated lipid antigen and superantigen to contact immunocyte activation receptors specific for tumor associated lipid antigens and superantigens in which inhibitory receptors or ITIMs which inhibit said cell activation by receptors specific for lipid-based tumor associated antigens are inactivated or deleted.
A method for producing a tumoricical immunocyte population ex vivo, said method comprising:
A method of producing a immunocyte population effective against infectious disease in a mammal in vivo said method comprising:
A method for producing an immunocyte population effective against infectious disease in a mammal ex vivo, said method comprising:
The superantigen of any of the claims wherein said superantigen is expressed by a tumor cell or accessory cell which has been transfected with a nucleic acid encoding a superantigen.
A mammalian cell wherein inhibitory receptors or their ITIMs and Fas ligand receptors are deleted or functionally inactivated
A method of treating cancer by wherein lipid-based tumor associated antigen or superantigen agonist motifs selectively contact immunocyte activating receptors and not immunocyte inhibitory receptors in vivo thereby producing an immunocyte population which is effective in the treatment of cancer.
A method of treating cancer by wherein lipid-based tumor associated antigen or superantigen agonist motifs selectively contact immunocyte activating receptors and not immunocyte inhibitory receptors ex vivo thereby producing an immunocyte population which is administered to the host and is effective in the treatment of cancer.
A method of treating infectious disease wherein lipid based infectious disease associated antigen agonist motifs selectively contact immunocyte activating receptors and not immunocyte inhibitory receptors in vivo thereby producing an immunocyte population effective in the treatment of infectious disease.
A method of treating infectious disease wherein lipid-based infectious disease associated antigens or superantigen agonist motifs selectively contact immunocyte activating receptors and not immunocyte inhibitory receptors ex vivo thereby producing an immunocyte population which is administered to the host and is effective in the treatment of infectious disease.
A method of treating infectious disease wherein lipid-based tumor associated antigens, lipid-based infectious disease associated antigens or superantigen antagonist motifs are deleted or blocked from contact with immunocyte inhibitory receptors thereby allowing agonist motifs to stimulate immunocyte activating receptors to produce an immunocyte population which is effective in the treatment of cancer or infectious disease.
A method of treating cancer and infectious disease according to claims wherein the immunocytes are transfected with HSV thymidine kinase gene which induces immunocyte death in vivo in response to exogenous administration of gancyclivir.
An mammalian antigen presenting cell wherein MHC class I molecules molecules of said cell are deleted or inactivated rendering said cell capable of presenting tumor associated lipid antigens and superantigens to immunocytes which are then capable of inducing a tumoricidal response,
An mammalian antigen presenting cell wherein MHC class I molecules molecules of said cell are deleted or inactivated rendering said cell capable of presenting infectious disease associated lipid antigens and superantigens to immunocytes which induce an effective response against infectious disease.
A mammalian cell comprising a fusion of a tumor cell with a mammalian cell whereby said fusion cell expresses glycosylceramides and tumor antigens.
A mammalian cell comprising a fusion of a tumor cell with a mammalian or invertebrate cell whereby said fusion cell expresses tumor antigens and phytosphingolipids.
A pharmacuetical composition useful in treatment of cancer comprising a lipid-based tumor associated antigen conjugated to a superantigen.
A pharmaceutical preparation useful in the treatment of infectious disease comprising a lipid-based infectious disease associated antigen conjugated to a superantigen
A pharmacuetical composition useful in the treatment of cancer comprising a tumor associated glycan antigen conjugated to a superantigen.
Dependencies are inferred from the claim text.