Ubivac, LLC

Providence Health & Services - Oregon

Providence Health System

Providence Health & Science—oregon

State of Oregon

Hong-Ming Hu

Bernard A Fox

Christopher Twitty

Rieneke Van De Ven

Traci Hilton

Christopher Paustian

Tarsem Moudgil

Sandra Aung

Christopher Dubay

Haiyan Li

Erik LeShane

Guangjie Yu

Jun Jiao

A method is presented for screening cells that produce allogeneic autophagosome enriched compositions able to induce expression of a selective marker on a subpopulation of peripheral blood mononuclear cells, the method comprising contacting a cell with a proteasome inhibitor, contacting the cell with a lysosome inhibitor, harvesting the resulting autophagosomes, determining a molecular signature of the harvested autophagosomes, and selecting cells that divert one or more Toll-like receptor agonist and/or one or more molecular chaperones to the harvested autophagosomes. By screening for cells that divert one or more Toll-like receptor agonist and/or one or more molecular chaperones to the harvested autophagosomes, enriched populations of autophagosomes may be generated which may illicit a specific immune response against numerous cancer types. In this way, an allogeneic, off-the-shelf cancer vaccine may be produced and made available to be administered in order to stimulate a targeted immune response in patients bearing different tumor types.

Allogeneic autophagosome-enriched composition for the treatment of disease

A method of inducing a specific immune response in a mammal, comprising: providing a first composition comprising isolated ubiquitinylated proteins in solution in the absence of membrane bound organelles, the isolated ubiquitinylated proteins comprising one or more specific antigens, and further comprising a threshold quantity of polyubiquitinylated short-lived proteins and polyubiquitinylated defective ribosomal products. The isolated ubiquitinylated proteins are affinity-purified from tumor-derived cells grown in culture, the tumor-derived cells being inhibited from degrading ubiquitinylated proteins via the proteasome while being grown in culture. In this way, highly immunogenic short-lived proteins and defective ribosomal products may be loaded onto dendritic cells for cross-presentation and priming of antigen-specific T cells restricted by either classical or non-classical MHC.

Ubiquitinylated proteins

A composition, comprising: an enriched population of autophagosomes derived from a non-small cell lung carcinoma cell line, and wherein the enriched population of autophagosomes includes: one or more toll-like receptor agonists; one or more tumor antigens; and one or more damage-associated molecular pattern molecules. In this way, an off-the-shelf vaccine may be available to be administered in order to stimulate a targeted immune response in patients bearing different tumor types.

Methods are disclosed for producing defective ribosomal products (DRiPs) in blebs (DRibbles) by contacting cells with a proteasome inhibitor, and in some examples also an autophagy inducer, thereby producing treated cells. DRibbles can be used to load antigen presenting cells (APCs), thereby allowing the APCs to present the DRiPs and antigenic fragments thereof. Immunogenic compositions that include treated cells, isolated DRibbles, or DRibble-loaded APCs are also disclosed. Methods are also provided for using treated cells, isolated DRibbles, or DRibble-loaded APCs to stimulate an immune response, for example in a subject. For example, DRibbles obtained from a tumor cell can be used to stimulate an immune response against the same type of tumor cells in the subject. In another example, DRibbles obtained from a pathogen-infected cell or cell engineered to express one or more antigens of a pathogen can be used to stimulate an immune response against the pathogen in the subject.

Defective ribosomal products in blebs (DRibbles) and methods of use to stimulate an immune response

Growing community of inventors

Portland, OR, United States of America

Hong-Ming Hu