Provided is a method of treating a cancer in an individual using activated T cells or PBMCs induced by antigen presenting cells (such as dendritic cells) loaded with a plurality of tumor antigen peptides. The method may further comprise administration of the antigen presenting cells loaded with the plurality of tumor antigen peptides to the individual. The methods may be used singly or in combination with an immune checkpoint inhibitor. Also provided are precision therapy methods customized for the individual using neoantigen peptides or based on the mutation load in the tumor of the individual, methods of preparing the activated T cells, methods of monitoring the treatment, methods of cloning tumor-specific T cell receptors, an isolated population of cells comprising the activated T cells, and compositions and kits useful for cancer immunotherapy.

The present invention relates to a method of treating or preventing an infection, a neoplastic disease or an immune-related disease in a subject in need thereof, the method comprising contacting a therapeutically effective or immuno-effective amount of an TLR9 agonist, specifically CpG oligodeoxynucleotide 2216 (CpG ODN), with a precursor dendritic cell (pre-DC), wherein the TLR9 agonist stimulates the pre-DC to secrete one or more cytokines such as TNF-alpha and IL-12p40, to thereby activate or increase the subject's immune response for treating or preventing the infection, the neoplastic disease or the immune-related disease. The present invention also relates to immunogenic or adjuvant compositions comprising the TLR9 agonist. A method of diagnosing a deficient immune system in a subject, comprising contacting a sample comprising pre-DC from the subject with one or more TLR 9 agonists and kits thereof are also disclosed.

The present invention relates to an accelerated method to generate high yields of type-1 polarizing mRNA loaded dendritic cells for use in immunotherapy, and in particular for use in cancer vaccination.

Cell culture systems and methods provide improved immunotherapeutic product manufacturing with greater scalability, flexibility, and automation. Cell culture systems are configured with interchangeable cartridges, allowing versatility and scalability. Systems are configured to have multiple connected cell culture chambers, which allows parallel processing of different types of cells. Gas-impermeable cell culture chambers and methods for generating cells in closed systems prevent contamination and user error. Methods for recycling cell culture medium provide additional efficiencies.

Cell culture systems and methods provide improved immunotherapeutic product manufacturing with greater scalability, flexibility, and automation. Cell culture systems are configured with interchangeable cartridges, allowing versatility and scalability. Systems are configured to have multiple connected cell culture chambers, which allows parallel processing of different types of cells. Gas-impermeable cell culture chambers and methods for generating cells in closed systems prevent contamination and user error. Methods for recycling cell culture medium provide additional efficiencies.

The present invention discloses novel methods, uses thereof, and compositions for modulating immune responses and homeostasis in a lymph node (LN). Moreover, structural and molecular characteristics of LN-innervating sensory neurons are provided. The present invention also discloses the target cells for LN-innervating sensory neurons in LN and molecular profiles of these target cells. These molecular characteristics provide therapeutic targets for modulating immune response and immune homeostasis in LN in an animal or a human.

In some aspects, disclosed are methods and compositions for disc regeneration and/or repair using one or more components from conditioned media from fibroblasts. In certain cases, conditioned media is obtained from fibroblasts stimulated with one or more opioid receptor antagonists and one or more toll-like receptor agonists. Conditioned media from fibroblasts may be provided in an effective amount to an individual in need thereof.

Methods are provided for treating blood monocytes to produce functional antigen presenting dendritic cells. An extracorporeal quantity of a subject's blood is treated to separate the blood and produce a leukocyte concentrate comprising monocytes and plasma containing proteins. The leukocyte concentrate comprising monocytes and plasma containing proteins is pumped through a plastic treatment device, such as a photopheresis device. The resulting treated cells may be incubated for a sufficient period of time to allow the monocytes to form dendritic cells, or the treated cells may be reinfused directly to the subject.

The invention pertains to a cell population for use in treating cancer in a patient, comprising CD1c (BDCA-1).sup.+/CD19.sup. dendritic cells, wherein CD1c(BDCA-1).sup.+/CD19.sup. dendritic cells are depleted for CD1c (BDCA-1).sup.+/CD19.sup./CD14.sup.+ cells.

The present invention relates to a method for determining the potency of DCs, comprising the steps: stimulating dendritic cells by incubation with soluble CD40L and TLR7/8 agonist, measuring the secretion of the marker proteins IL-10 and IL-12 from the stimulated dendritic cells. Thereby it can be determined whether the dendritic cell have a high capability to activate T-cells and Natural Killer (NK) cells. The invention also encompasses a method for stimulating dendritic cells comprising the step of stimulating the dendritic cells with soluble CD40L and TLR7/8 agonist.