Immunicom, Inc.

National Institutes of Health, a Component of the US Dept. of Health & Human Services

Steven Francis Josephs

Amir Jafri

Mark Raptis

Stephen Michael Prince

Robert Segal

Robert C Gallo

Flossie Wong-Staal

Carl W Saxinger

Annette Marleau

Syed Z Salahuddin

Dharam V Ablashi

Thomas Emanuel Ichim

David L Schlotterbeck

Matthew Ong

Michael Matho

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.

Modified TNF as a capture ligand

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.

Increasing responses to checkpoint inhibitors by extracorporeal apheresis

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.

Reduced leaching of a ligand

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&#x3b1;. The system and method are useful for the treatment of different cancer types, stages and severity.

System and method for removal of immune inhibitors from biological fluids

A new human B lymphotropic virus, also designated human herpesvirus-6, has been isolated. DNA, molecular clones, antigenic viral proteins and antibodies having specificity to the new virus have been prepared. Various utilities of the new virus and products derived therefrom have been described.

Antibodies against human herpes virus-6(HHV-6) and method of use

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San Diego, CA, United States of America

Steven Francis Josephs