The present invention relates to a phenotypically distinct CD1d.sup.highCD5.sup.+ B cell subset that regulates T cell mediated inflammatory responses through the secretion of interleukin-10 (IL-IO). The invention also relates to the use of these IL-IO producing regulatory B cells in the manipulation of immune and inflammatory responses, and in the treatment of disease. Therapeutic approaches involving adoptive transfer of these regulatory B cells, or expansion of their endogenous levels for controlling autoimmune or inflammatory diseases and conditions are described. Ablation of this subset of regulatory B cells, or inhibition of their IL-IO production can be used to upregulate immunodeficient conditions, and/or to treat tumors/cancer. Diagnostic applications also are encompassed.

The current invention provides monocytic cells transfected with chimeric antigen receptor (CAR) to selectively home to tumors and upon homing differentiate into dendritic cells capable of activating immunity which is inhibitory to said tumor. In one embodiment of the invention, monocytic cells are transfected with a construct encoding an antigen binding domain, a transcellular or structural domain, and an intracellular signaling domain. In one specific aspect of the invention, the antigen binding domain interacts with sufficient affinity to a tumor antigen, capable of triggering said intracellular domain to induce an activation signal to induce monocyte differentiation into DC.

The present invention relates to compositions and methods that provide novel therapies in cancer. The invention includes a phagocytic cell modified with a repressor of signal regulatory protein-alpha (SIRP) and bound to a targeting antibody to enhance phagocytic activity of the phagocytic cell toward tumor tissue. Methods of enhancing phagocytic activity and treating a tumor are also included.

The present invention relates to a composition comprising a supernatant of a peripheral blood mononuclear cell (PBMC) cell culture for use in the treatment or prevention of vasculitis, wherein the PCBMC cell culture comprises 110.sup.5 to 110.sup.8 PBMCs/ml and is subjected to radiation before or during cultivation and cultivated for at least 4 h.

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).

The present invention relates to a polypeptide for delivering an antigen to immune cells and, specifically, to: a novel polypeptide comprising a cell membrane penetrating peptide and a peptide binding to a surface molecule on immune cells; a fusion polypeptide in which an antigen is coupled to the polypeptide; a nucleic acid coding for the polypeptide or the fusion polypeptide; an immune cell sensitized with the fusion polypeptide or the nucleic acid coding therefor; and an immunotherapeutic agent, antitumor or anticancer vaccine, and a composition for treating a tumor or cancer, each comprising the immune cell.

An immune checkpoint (PD-L1) inhibitor oligopeptide comprising the sequence GTRLKPLIICVQWPGL (SEQ ID NO:1), nucleic acids encoding the oligopeptide, and vectors and cells for delivery nucleic acids encoding the oligopeptide are disclosed. Methods of treating cancer and enhancing anti-tumor immunity are also disclosed.

Disclosed are methods of isolating T cells having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation, the method comprising: identifying one or more genes in the nucleic acid of a cancer cell of a patient, each gene containing a cancer-specific mutation that encodes a mutated amino acid sequence; inducing autologous APCs of the patient to present the mutated amino acid sequence; co-culturing autologous T cells of the patient with the autologous APCs that present the mutated amino acid sequence; and selecting the autologous T cells. Also disclosed are related methods of preparing a population of cells, populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer.

Disclosed are methods of treating or preventing cancer in a mammal, the method comprising: (a) isolating T cells from a tumor sample from the mammal, wherein the isolated T cells are one or both of exhausted and differentiated, and the isolated T cells have antigenic specificity for a tumor-specific antigen expressed by the tumor sample from the mammal, wherein the tumor-specific antigen is a tumor-specific neoantigen or an antigen with a tumor-specific driver mutation; and optionally expanding the numbers of isolated, tumor antigen-specific T cells; and (b) administering to the mammal (i) the isolated T cells of (a) and (ii) a vaccine which specifically stimulates an immune response against the tumor-specific antigen for which the isolated T cells have antigenic specificity.

The present invention provides, in some embodiments, methods, compositions, systems, and kits comprising nano-satellite complexes comprising: a core nanoparticle complex comprising a biocompatible coating surrounding a nanoparticle core; 3-25 satellite particles attached to, or absorbed to, said biocompatible coating; a plurality of antigenic peptides conjugated to, or absorbed to, said satellite particles; and at least one additional property. In other embodiments, provided herein are nano-satellite complexes comprising: a core nanoparticle complex comprising a biocompatible coating surrounding a nanoparticle core; a plurality of satellite particles attached to, or absorbed to, said biocompatible coating; a plurality of antigenic peptides conjugated to, or absorbed to, said satellite particles; and a plurality of LIGHT (TNFSF14) peptides conjugated to, or absorbed to, said satellite particles. In some embodiments, administration of the nanosatellite complexes to a subject with cancer achieves long-term cancer remission (e.g., when combined with an immune checkpoint inhibitor, such as PD1).