Adenoviral Vector Transduced Apheresis Product
AssigneeImmunityBio, Inc.
InventorsPatrick Soon-Shiong, Elizabeth Gabitzsch
Life of this patent
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Abstract
An immunotherapeutic composition is contemplated that comprises subject-derived peripheral blood mononuclear cells (PBMC) and at least one recombinant adenovirus subtype 5 (Ad5) comprising a deletion in an E1 gene region, a deletion in an E2b gene region, and a nucleic acid sequence encoding a peptide antigen, wherein the PBMC are exposed ex-vivo to the at least one Ad5 vector. Advantageously, the same PBMC composition may also be used to prepare modified NK cells, and especially modified NK include CIML NK cells, CENK cells and mCENK cells.
Claims20
An immunotherapeutic composition, comprising:
- subject-derived peripheral blood mononuclear cells (PBMC);
- and
- at least one recombinant adenovirus subtype 5 (Ad5) vector comprising a deletion in an E1 gene region, a deletion in an E2b gene region, and a nucleic acid sequence encoding a peptide antigen, wherein the PBMC are exposed ex-vivo to the at least one Ad5 vector.
A method of treatment of cancer or infectious disease, the method comprising:
- performing therapeutic apheresis on a subject;
- purifying the peripheral blood mononuclear cell (PBMC) fraction from the apheresis product;
- exposing ex vivo the PBMC to at least one recombinant adenovirus subtype 5 (Ad5) vector comprising a deletion in an E1 gene region, a deletion in an E2b gene region, and a nucleic acid sequence encoding a peptide antigen of the cancer or a pathogen that causes the infectious disease;
- and
- administering an effective amount of the Ad5 vector treated PBMC to a patient.
A method of transfecting a plurality of peripheral blood mononuclear cells (PBMC), the method comprising the following steps in sequence:
- (1) providing an ex vivo prepared PBMC fraction, wherein the PBMC fraction contains in addition to antigen presenting/dendritic cells, cells selected form the group consisting of macrophages, monocytes, T cells, and B cells;
- (2) exposing the PBMC fraction to GM-CSF and Flt3L to trigger differentiation of the antigen presenting/dendritic cells;
- (3) exposing ex vivo the PBMC fraction to recombinant adenovirus subtype 5 (Ad5) viral particles at a multiplicity of infection (MOI) of at least 100, wherein the recombinant Ad5 particles comprise a deletion in an E1 gene region, a deletion in an E2b gene region, and a nucleic acid sequence encoding a peptide antigen of a cancer or a pathogen that causes an infectious disease;
- (4) expanding T cells in the PBMC fraction using IL-2, IL-7, and IL-15;
- (5) re-exposing the ex vivo the PBMC fraction to the recombinant adenovirus subtype 5 (Ad5) viral particles;
- and
- (6) placing the re-exposed PBMC fraction into a medium suitable for transfusion.
Dependencies are inferred from the claim text.