The embodiment of the invention is to enable universal non-classical MHC I peptide vaccines restricted to HLA-E, HLA-F and HLA-G. An algorithm was develop to predict HLA-E binding immunogenic or suppressorgenic peptides of the autologous origins, e.g., autoantigens, inflammatory antigens, IgE and cancer antigens, and of the microbial origins. Thus, the embodiment of the invention is to load the antigenic peptides of medical and therapeutic importance onto the non-polymorphic HLA-E, HLA-F, and HLA-G culminating in universal vaccines, bypassing highly polymorphic classical MHC I, e.g., HLA-A, HLA-B and HLA-C pathways, in order to treat autoimmune diseases, allergy, inflammatory diseases, cancers, and infectious diseases for all human population. Derlin-1 and UL40 pathways are utilized to enable antigen presentation and vaccine efficacies in the non-classical MHC I pathways.

The embodiment of the invention is to enable universal non-classical MHC I peptide vaccines restricted to HLA-E, HLA-F and HLA-G. An algorithm was develop to predict HLA-E binding immunogenic or suppressorgenic peptides of the autologous origins, e.g., autoantigens, inflammatory antigens, IgE and cancer antigens, and of the microbial origins. Thus, the embodiment of the invention is to load the antigenic peptides of medical and therapeutic importance onto the non-polymorphic HLA-E, HLA-F, and HLA-G culminating in universal vaccines, bypassing highly polymorphic classical MHC I, e.g., HLA-A, HLA-B and HLA-C pathways, in order to treat autoimmune diseases, allergy, inflammatory diseases, cancers, and infectious diseases for all human population. Derlin-1 and UL40 pathways are utilized to enable antigen presentation and vaccine efficacies in the non-classical MHC I pathways.

Devices, systems, and methods can be used for the automated production of dendritic cells (DC) from dendritic cell progenitors, such as monocytes obtained from peripheral blood. The invention makes it possible to obtain sufficient quantities of a subject's own DC for use in preparing and characterizing vaccines, for activating and characterizing the activation state of the subject's immune response, and to aid in preventing and/or treating cancer or infectious disease.

Devices, systems, and methods can be used for the automated production of dendritic cells (DC) from dendritic cell progenitors, such as monocytes obtained from peripheral blood. The invention makes it possible to obtain sufficient quantities of a subject's own DC for use in preparing and characterizing vaccines, for activating and characterizing the activation state of the subject's immune response, and to aid in preventing and/or treating cancer or infectious disease.

TNFR2-expressing neuroblastoma cells activate monocytes via contact-dependent mTNFα signaling, leading to production of sTNFα and IL-6 by monocytes that in turn bind to TNFR1 and IL-6R on neuroblastoma cells and stimulate tumor growth via activation of NF-κB and Sta3 signaling pathways. Growing tumor recruit additional monocytes resulting in a self-promoting inflammation that fuel tumor growth. TNF inhibitors can terminate this feed-forward signal amplification loop and inhibit tumor growth. Embodiments of the disclosure include a method of using TNF inhibitors for the treatment of neuroblastoma in a subject in need thereof. Also disclosed herein is a method of a method of using TNF inhibitors for reducing tumor-promoting inflammation in an individual with cancer.

A trifunctional molecule comprising a target-specific ligand, a ligand that binds a protein associated with the TCR complex and a T cell receptor signaling domain polypeptide is provided. The ligand that binds a protein associated with a TCR complex is UCHT1 with a Y182T mutation. Engineering T cells with this novel receptor engenders antigen specific activation of numerous T cell functions, including cytokine production, degranulation and cytolysis.

A trifunctional molecule comprising a target-specific ligand, a ligand that binds a protein associated with the TCR complex and a T cell receptor signaling domain polypeptide is provided. The ligand that binds a protein associated with a TCR complex is UCHT1 with a Y182T mutation. Engineering T cells with this novel receptor engenders antigen specific activation of numerous T cell functions, including cytokine production, degranulation and cytolysis.

The present disclosure provides immunomodulatory fusion proteins-metal hydroxide complexes comprising an immunomodulatory domain adsorbed to a metal hydroxide via ligand exchange. The disclosure also features compositions and methods of using the same, for example, to treat cancer.

The present disclosure provides immunomodulatory fusion proteins-metal hydroxide complexes comprising an immunomodulatory domain adsorbed to a metal hydroxide via ligand exchange. The disclosure also features compositions and methods of using the same, for example, to treat cancer.

The present invention relates, in part, to agents that bind CD8 and their use as therapeutic and diagnostic agents. The present invention further relates to pharmaceutical compositions comprising the CD8 binding agents and their use in the treatment of various diseases, including, for example, cancers.