Abstract: A column is disclosed for removal of sTNF-R2 from a body fluid. The column has a compartment, an inlet coupled to the compartment and configured to receive the body fluid, and a substrate disposed within the compartment. A capture ligand is coupled to the substrate and has a modified sequence with an amino acid substitution in a reference sequence that includes a portion of a natural TNF sequence. The modified sequence has an affinity for the sTNF-R2 that is greater than an affinity of the reference sequence for the sTNF-R2.

Abstract: The invention provides means, methods, and compositions of matter useful for enhancing tumor response to checkpoint inhibitors. In one embodiment, the invention teaches utilization of extracorporeal apheresis, specifically removal of various tumor derived, or tumor microenvironment derived immunological “blocking factors”. In one embodiment the invention provides the removal of soluble TNF-alpha receptors (sTNF-Rs) as a means of augmenting efficacy of immune checkpoint inhibitors. In one specific embodiment removal of sTNF-Rs is utilized to enhance efficacy of inhibitors of the PD-1/PD-L1 pathway, and/or the CD28/CTLA-4 pathway.

Abstract: A column is disclosed for removal of sTNF-R2 from a body fluid. The column has a compartment, an inlet coupled to the compartment and configured to receive the body fluid, and a substrate disposed within the compartment. A capture ligand is coupled to the substrate and has a modified sequence with an amino acid substitution in a reference sequence that includes a portion of a natural TNF sequence. The modified sequence has an affinity for the sTNF-R2 that is greater than an affinity of the reference sequence for the sTNF-R2.

Abstract: A column for removal of a component from a fluid is disclosed. The column has a compartment with a cross sectional area. The compartment contains beads having a diameter. A ligand selected to bind to the component is coupled to the beads. The cross-sectional area and bead diameter are selected to maintain a flow velocity of the fluid within the compartment below a first threshold, thereby reducing leaching of the ligand into the fluid. Also described herein is an adsorbent comprising a ligand that is attached to a substrate by an amine bond, wherein the ligand is resistant to dissociation from the substrate.

Abstract: Disclosed are means, methods and compositions of matter useful for amplification of adaptive immune responses towards neoplastic tissue. In one embodiment, immunization of a patient is performed by a means comprising of administering either an exogenous vaccine or stimulation of immunogenicity of the tumor so as to cause release of antigens/increased exposure of antigens, thus resulting in an “endogenous” vaccine. Subsequent to vaccination a patient is treated by an immunopheresis procedure, in order to allow for removal of “blocking factors” produced by the tumor or produced by cells programmed by tumors to produce said blocking factors. In one embodiment further immunization is performed subsequent to removal of said blocking factors in order to allow for enhancement of adaptive immune responses.

Abstract: The invention provides means, methods, and compositions of matter useful for enhancing tumor response to checkpoint inhibitors. In one embodiment, the invention teaches utilization of extracorporeal apheresis, specifically removal of various tumor derived, or tumor microenvironment derived immunological “blocking factors”. In one embodiment the invention provides the removal of soluble TNF-alpha receptors (sTNF-Rs) as a means of augmenting efficacy of immune checkpoint inhibitors. In one specific embodiment removal of sTNF-Rs is utilized to enhance efficacy of inhibitors of the PD-1/PD-L1 pathway, and/or the CD28/CTLA-4 pathway.

Abstract: Disclosed are means, methods and compositions of matter useful for amplification of adaptive immune responses towards neoplastic tissue. In one embodiment, immunization of a patient is performed by a means comprising of administering either an exogenous vaccine or stimulation of immunogenicity of the tumor so as to cause release of antigens/increased exposure of antigens, thus resulting in an “endogenous” vaccine. Subsequent to vaccination a patient is treated by an immunopheresis procedure, in order to allow for removal of “blocking factors” produced by the tumor or produced by cells programmed by tumors to produce said blocking factors.

Abstract: Disclosed are means, methods and compositions of matter useful for amplification of adaptive immune responses towards neoplastic tissue. In one embodiment, immunization of a patient is performed by a means comprising of administering either an exogenous vaccine or stimulation of immunogenicity of the tumor so as to cause release of antigens/increased exposure of antigens, thus resulting in an “endogenous” vaccine. Subsequent to vaccination a patient is treated by an immunopheresis procedure, in order to allow for removal of “blocking factors” produced by the tumor or produced by cells programmed by tumors to produce said blocking factors.

Abstract: The invention provides means, methods, and compositions of matter useful for enhancing tumor response to checkpoint inhibitors. In one embodiment, the invention teaches utilization of extracorporeal apheresis, specifically removal of various tumor derived, or tumor microenvironment derived immunological “blocking factors”. In one embodiment the invention provides the removal of soluble TNF-alpha receptors (sTNF-Rs) as a means of augmenting efficacy of immune checkpoint inhibitors. In one specific embodiment removal of sTNF-Rs is utilized to enhance efficacy of inhibitors of the PD-1/PD-L1 pathway, and/or the CD28/CTLA-4 pathway.

Abstract: The invention provides means, methods, and compositions of matter useful for enhancing tumor response to checkpoint inhibitors. In one embodiment, the invention teaches utilization of extracorporeal apheresis, specifically removal of various tumor derived, or tumor microenvironment derived immunological “blocking factors”. In one embodiment the invention provides the removal of soluble TNF-alpha receptors (sTNF-Rs) as a means of augmenting efficacy of immune checkpoint inhibitors. In one specific embodiment removal of sTNF-Rs is utilized to enhance efficacy of inhibitors of the PD-1/PD-L1 pathway, and/or the CD28/CTLA-4 pathway.

Abstract: The invention provides means, methods, and compositions of matter useful for enhancing tumor response to checkpoint inhibitors. In one embodiment, the invention teaches utilization of extracorporeal apheresis, specifically removal of various tumor derived, or tumor microenvironment derived immunological “blocking factors”. In one embodiment the invention provides the removal of soluble TNF-alpha receptors (sTNF-Rs) as a means of augmenting efficacy of immune checkpoint inhibitors. In one specific embodiment. removal of sTNF-Rs is utilized to enhance efficacy of inhibitors of the PD-1/PD-L1 pathway, and/or the CD28/CTLA-4 pathway.

Abstract: A column for removal of a component from a fluid is disclosed. The column has a compartment with a cross sectional area. The compartment contains beads having a diameter. A ligand selected to bind to the component is coupled to the beads. The cross-sectional area and bead diameter are selected to maintain a flow velocity of the fluid within the compartment below a first threshold, thereby reducing leaching of the ligand into the fluid. Also described herein is an adsorbent comprising a ligand that is attached to a substrate by an amine bond, wherein the ligand is resistant to dissociation from the substrate.

Abstract: The present system and method are useful for the removal of immune inhibitors such as soluble TNF receptors from the body fluid of cancer patients. In some embodiments, soluble TNF-Receptors 1 and 2 are selectively removed from plasma at 80% or more efficiency. In some embodiments, the system includes an immobilized capture ligand of a single chain TNF?. The system and method are useful for the treatment of different cancer types, stages and severity.

Abstract: The invention provides means, methods, and compositions of matter useful for enhancing tumor response to checkpoint inhibitors. In one embodiment, the invention teaches utilization of extracorporeal apheresis, specifically removal of various tumor derived, or tumor microenvironment derived immunological “blocking factors”. In one embodiment the invention provides the removal of soluble TNF-alpha receptors (sTNF-Rs) as a means of augmenting efficacy of immune checkpoint inhibitors. In one specific embodiment removal of sTNF-Rs is utilized to enhance efficacy of inhibitors of the PD-1/PD-L1 pathway, and/or the CD28/CTLA-4 pathway.

Abstract: The invention provides means, methods, and compositions of matter useful for enhancing tumor response to checkpoint inhibitors. In one embodiment, the invention teaches utilization of extracorporeal apheresis, specifically removal of various tumor derived, or tumor microenvironment derived immunological “blocking factors”. In one embodiment the invention provides the removal of soluble TNF-alpha receptors (sTNF-Rs) as a means of augmenting efficacy of immune checkpoint inhibitors. In one specific embodiment removal of sTNF-Rs is utilized to enhance efficacy of inhibitors of the PD-1/PD-L1 pathway, and/or the CD28/CTLA-4 pathway.

Abstract: Disclosed are means, methods and compositions of matter useful for amplification of adaptive immune responses towards neoplastic tissue. In one embodiment, immunization of a patient is performed by a means comprising of administering either an exogenous vaccine or stimulation of immunogenicity of the tumor so as to cause release of antigens/increased exposure of antigens, thus resulting in an “endogenous” vaccine. Subsequent to vaccination a patient is treated by an immunopheresis procedure, in order to allow for removal of “blocking factors” produced by the tumor or produced by cells programmed by tumors to produce said blocking factors.