Adenoviral vector transduced apheresis product
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.
1. An immunotherapeutic composition, comprising:
1) Subject-derived peripheral blood mononuclear cells (PBMC), granulocyte macrophage colony stimulating factor (GM-CSF), and FMS-like tyrosine kinase 3 (Flt-3) ligand,
2) 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, and
2) Immune-stimulating cytokines comprising a) Interleukin-15 (IL-15) or an IL-15: IL-15 receptor alpha (IL15: IL15Rα) complex, b) IL-2, and c) IL-7,
wherein the PBMC are simultaneously exposed to the Ad5 vector and the immune stimulating cytokines.
2. The immunotherapeutic composition of claim 1 , wherein the IL15: IL15Rα complex comprises an IL-15N72D: IL15RαSu/Fc complex (N-803).
3. The immunotherapeutic composition of claim 1 , wherein the subject has been diagnosed with an infectious disease, a neoplastic disease, or cancer.
4. The immunotherapeutic composition of claim 3 , wherein the neoplastic disease or cancer comprises bladder cancer, a glioblastoma, prostate cancer, hematological cancer, B-cell neoplasms, multiple myeloma, B-cell lymphoma, Hodgkin's lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, cutaneous T-cell lymphoma, T-cell lymphoma, a solid tumor, urothelial/bladder carcinoma, melanoma, lung cancer, renal cell carcinoma, breast cancer, gastric and esophageal cancer, head and neck cancer, colorectal cancer, ovarian cancer, non-small cell lung carcinoma, B cell non-Hodgkin lymphoma, squamous cell head or neck carcinoma, or urothelial/bladder carcinoma.
5. The immunotherapeutic composition of claim 1 , wherein the PBMC comprise T cells, natural killer (NK) cells, natural killer T (NK-T) cells, dendritic cells, mast cells, myeloid derived phagocytes or combinations thereof.
6. The immunotherapeutic composition of claim 1 , wherein the immunotherapeutic composition is formulated for intravenous (IV) administration.