Abstract: Cancer is treated using coordinated treatment regimens that uses various compounds and compositions that drive a tumor from the escape phase of cancer immunoediting to the elimination and equilibrium phase of cancer immunoediting.

Abstract: Techniques are provided for determining pan-HLA binding of viral proteins. A trained classifier model is operable to determine, independently per HLA, at least one of (a) an average binding prediction of overlapping peptides at each position of a viral protein, (b) a maximum value of a binding prediction of overlapping peptides at each position of the viral protein, (c) standard deviation of a binding prediction of overlapping peptides at each position of the viral protein, and (d) a combination of one or more of (a)-(c). A classification engine uses the classifier model to determine average binding predictions of overlapping peptides at each position of the viral protein independently for test HLA-I and HLA-II functional groupings, where a peptide is classified as a binder when an average binding prediction corresponding to the peptide satisfies a binding value threshold.

Abstract: Combination therapeutics for the treatment of cancer include the use of immune effector cells, IL-15 based superagonists and one or more immunotherapeutic agents such as Bacillus Calmette-Guerin (BCG).

Abstract: Systems and methods are presented that provide for improved NK cell function. In preferred aspects, NK-92 cells express recombinant er/LSP-IL-15 to so render the NK-92 cells independent of exogenous cytokines and to provide extracellular immune stimulation.

Abstract: Methods and pharmaceutical combinations for preventing, reducing the occurrence of, and/or treating an infection in a subject are provided herein. The method includes administering to the subject a therapeutically effective amount of an IL-15 agonist after or concomitantly with administration of a therapeutically effective amount of an antibiotic to the subject. The pharmaceutical combination includes an IL-15 agonist and an antibiotic.

Abstract: HIV treatment, and especially treatment of latent infected CD4 cells, can be significantly improved using a kick-and-kill approach that employs an immune stimulation component and/or HDAC inhibition as one treatment component, and that may also include a second component in which a vaccine composition, various NK cells, CAR-T cells, and/or broadly neutralizing antibodies are administered.

Abstract: An apparatus for electroporating cells with a cargo includes electrodes defining a path for a fluid including the cells and the cargo to flow, a power source coupled across the electrodes, and a control circuit. In some examples, the control circuit is configured to detect a decrease in an induced current due to an increase in a resistance between the electrodes, and control the power source to increase the induced current to maintain an electric field between the electrodes. A future value of the resistance between the electrodes may be predicted based on previous values of the resistance. In other examples, the control circuit is configured to detect parameters of the fluid flowing between the electrodes, and control the power source to generate or stop generating electrical pulses in response to detecting the parameters. Other example apparatuses, and methods of electroporating cells with a cargo is also disclosed.

Abstract: Contemplated treatments and methods produce substantially increased quantities of memory T-cells and a persistent immune response by subcutaneous and/or subdermal co-administration of (1) a vector comprising a recombinant nucleic acid that encodes a cancer associated epitope, a cancer specific epitope, and/or a neoepitope, (2) an immune stimulating cytokine, and (3) a checkpoint inhibitor. Most typically, the co-administration is performed at substantially the same location, preferably within 1-21 days from each other, and the vector is an adenoviral expression vector, for example, included in a viral particle such as an AdV5 virus with a deletion of the E2b gene.

Abstract: Detection of under-expression of selected genes in NK cells is used to confirm a hypoxic tumor microenvironment that is ordinarily suppressive with respect to ADCC and cytotoxic cell killing of NK cells. Most notably, while hypoxia is known to upregulate HIF-1? and genes under the control of HIF-1?, hypoxia in a tumor microenvironment led to under-expression of selected genes, including HIF-1?. Thus, gene expression analysis of certain genes on NK cells can be used to detect conditions in a tumor that would indicate use of haNK cells.

Abstract: Cancer is treated using coordinated treatment regimens that uses various compounds and compositions that drive a tumor from the escape phase of cancer immunoediting to the elimination and equilibrium phase of cancer immunoediting.

Abstract: The invention features multi-specific protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to a disease antigen, immune checkpoint or signaling molecule.

Abstract: A cancer vaccine is provided including a recombinant nucleic acid encoding a self-activating chimeric signaling protein, and especially chimeric TNF family ligand-receptor proteins, and a tumor-associated antigen. In a preferred embodiment, the cancer vaccine may further include a nucleic acid segment encoding an IL-15 superagonist. In addition, the cancer vaccine can be co-administered with a genetically modified bacteria or yeast as an adjuvant to increase the payload expression of the cancer vaccine. Advantageously, cells expressing such combination of molecules will enhance immune reaction against tumor cells. Compositions and methods are presented that allow for an enhanced immune response against a vaccine composition, and particularly a recombinant adenoviral expression system that is used as a therapeutic agent. Most preferably, immune therapeutics are administered such that a protein or nucleotide are co-located with a therapeutic antigen, preferably via co-expression of the protein.

Abstract: Systems and methods are presented that allow for selection of tumor neoepitopes that are then used to generate a recombinant polytope that is optimized for proper trafficking and processing. In preferred methods, the polytope is encoded in a viral expression system that is used as a therapeutic agent.

Abstract: Cancer is treated using coordinated treatment regimens that uses various compounds and compositions that drive a tumor from the escape phase of cancer immunoediting to the elimination and equilibrium phase of cancer immunoediting.

Abstract: NK cell based cancer immunotherapy, and particularly genetically modified NK92 cell-based immunotherapy is enhanced by expression CXCL12 and/or by suppression or deletion of CXCR4 in the natural killer cells to so reduce aggregation, rejection, and/or fratricide of the natural killer cells. Provided herein are genetically engineered NK (natural killer) cell comprising a recombinant nucleic acid encoding at least a portion of chemokine C—X—C motif ligand 12 (CXCL12), and a transcript for downregulation of chemokine C—X—C motif receptor 4 (CXCR4).