Method of Ex Vivo Enhancement of Immune Cell Activity for Cancer Immunotherapy with a Small Molecule Ablative Compound

Abstract

A cancer immunotherapy method is disclosed in which “induced immune anticancer agents” are isolated after being induced in an animal host by intralesional (IL) administration of a halogenated xanthene tumor-ablative compound into a solid cancerous tumor of that host animal. A sample of the induced immune anticancer agents is removed (collected) from the tumor-bearing host, banked if desired, cultured and preferentially expanded to form an immunologically-effective enriched tumor-specific immune anticancer agent composition. That composition is reintroduced in to the host from which the predecessor induced immune anticancer agents were taken, or into another immunologically suitable host in need.

1 - 27 . (canceled) 
     
     
         28 . A tumor-specific immune anticancer agent composition whose components are induced by one or more intralesional (IL) administrations of a tumor-ablating amount of a halogenated xanthene compound into one or more solid cancerous tumors of a host mammal and collected from said host mammal about 1 to about 365 days after said one or more IL administrations, said composition, relative to an amount prior to said administration, comprising a statistically significantly enhanced concentration of halogenated xanthene-induced immune anticancer components that are one or more of a) a lymph-soluble cytokine selected from the group consisting of IL-2, TNF-α, LT, GM-CSF, IFN-γ,and HMGB1, b) immune cells that are peripheral blood mononuclear (PBM) cells and c) antibodies that bind to an antigen displayed on a whole tumor cell or chemoablated cell debris. 
     
     
         29 . The tumor-specific immune anticancer agent composition according to  claim 28  whose composition components include PBM immune cells obtained from said host mammal. 
     
     
         30 . The tumor-specific immune anticancer agent composition according to  claim 29 , wherein said PBM immune cells are selected from the group consisting of NK cells, T cells, dendritic cells and B cells. 
     
     
         31 . The tumor-specific immune anticancer agent composition according to  claim 28 , wherein said induced immune anticancer components include anti-tumor antibodies, antigen proteins and cytokine proteins. 
     
     
         32 . The tumor-specific immune anticancer agent composition according to  claim 31 , wherein said cytokines are selected from the group consisting of one or more IL-2, TNF-α, LT, GM-CSF, IFN-γ and HMGB1. 
     
     
         33 . The tumor-specific immune anticancer agent composition according to  claim 28  banked for further use. 
     
     
         34 . The tumor-specific immune anticancer agent composition according to  claim 28 , wherein the contacted cancerous tumor tissue is selected from one or more of the group consisting of melanoma, prostate, breast, bladder, renal, pancreatic, colon, colorectal, gall bladder, primary or metastatic liver cancer, and small cell and non-small cell lung cancer. 
     
     
         35 . The tumor-specific immune anticancer agent composition according to  claim 34 , wherein the contacted cancerous tumor tissue is melanoma. 
     
     
         36 . The tumor-specific immune anticancer agent composition according to  claim 28 , wherein a therapeutically effective amount of a monoclonal antibody that immunoreacts with one or more of CTLA-4, PD-1, PD-L1 and PD-L2 and is a systemic inhibitor of immune system down regulation is administered to said host animal after administration of said tumor-ablating amount of a halogenated xanthene and prior to collection of said tumor-specific immune anticancer agent composition. 
     
     
         37 . The tumor-specific immune anticancer agent composition according to  claim 36 , wherein said monoclonal antibody immunoreacts with one or more of CTLA-4 and PD-1. 
     
     
         38 . The tumor-specific immune anticancer agent composition according to  claim 28 , wherein said tumor-specific immune anticancer agent composition is collected after repeated IL administrations. 
     
     
         39 . The tumor-specific immune anticancer agent composition according to  claim 38 , wherein said tumor-specific immune anticancer agent composition is collected about 4 to about 90 days after said repeated IL administrations. 
     
     
         40 . An enriched tumor-specific immune anticancer agent preparation comprising the tumor-specific immune anticancer agent composition according to  claim 28  whose immune anticancer composition components have been cultured and preferentially expanded in vitro. 
     
     
         41 . The tumor-specific immune anticancer agent composition according to  claim 28  banked for further use. 
     
     
         42 . An immunologically-effective enriched tumor-specific immune anticancer agent preparation that contains an immunologically-effective concentration of an enriched tumor-specific immune anticancer agent preparation according to  claim 36  dissolved or dispersed in a pharmaceutically acceptable diluent, said preparation having a parental injection-appropriate pH value, salt content and osmolality. 
     
     
         43 . The immunologically-effective enriched tumor-specific immune anticancer agent preparation according to  claim 42  including one or more of NK cells, T cells, B cells and dendritic cells. 
     
     
         44 . The immunologically-effective enriched tumor-specific immune anticancer agent preparation according to  claim 42  including one or both of HMGB1 and IFN-γ.