The disclosure relates to compositions and methods of generating synthetic antigen receptors or SAR (e.g., SIR, zSIR, cTCR, ab-TCRs, AABD-TCRs, TFP, TACs etc.) and antibodies (e.g., bispecific antibodies, DARTs etc.) comprising one or more novel antigen binding domains. SARs as described comprise single chain immune receptors (e.g., 1.sup.st, 2.sup.nd and 3.sup.rd generation chimeric antigen receptors, TFPs. Tri-TAC and the like) and multiple chain immune receptors (e.g., SIR, zSIR, cTCR. ab-TCR. AABD-TCR. αβTFP, ydTFP, recombinant TCRs etc.). SARs are able to redirect immune cell specificity and reactivity toward one or more selected targets exploiting the antigen-binding domain properties.

The present invention is directed to a pharmaceutical composition including (e.g. for use as an adjuvant) a polymeric carrier cargo complex, comprising as a carrier a polymeric carrier formed by disulfide-crosslinked cationic components; and as a cargo at least one nucleic acid molecule, and at least one antigen that is selected from an antigen from a pathogen associated with infectious disease; an antigen associated with allergy or allergic disease; an antigen associated with autoimmune disease; or an antigen associated with a cancer or tumour disease, or in each case a fragment, variant and/or derivative of said antigen. The pharmaceutical composition allows for efficient induction of an adaptive immune response directed against said antigen. The present invention furthermore provides kits, as well as the use of the pharmaceutical composition or the kit as a vaccine, particularly in the treatment of infectious diseases, allergies, autoimmune diseases and tumour or cancer diseases.

Embodiments of the disclosure include methods and compositions useful for treating cancer in an immunogenic manner so as to elicit local tumor regression, while priming systemic immunity. In one embodiment, there is expansion of tumor-specific immune cells through administration of fibroblasts, either natural or modified in an intratumoral and/or peritumoral manner. In other embodiments, manipulation of a local tumor microenvironment is achieved by injections of immune-modulating fibroblasts to facilitate expansion of immune effector cells, which are subsequently re-stimulated in the periphery by antigenic exposure. In another embodiment, agents are provided that allow for systemic derepression of immunity, while optionally augmenting ability of immune effector cells to expand and kill tumor cells.

The present invention in general relates to combinations of mRNA molecules encoding CD40, caTLR4 and CD70 with mRNA molecules encoding tumor-associated antigens for use as therapeutic vaccine in the treatment of metastatic cancer patients primarily with stable malignant melanoma disease, but also extending into other cancer types and to patient whose disease has shown partial response on prior therapy. Said uses may further encompass the administration of checkpoint inhibitors. The present invention further provides administration schemes for such therapies focusing on administration of the therapeutic into lymph nodes, so called intra-nodal therapy.

Described herein are compositions and methods for treating cancer and autoimmune diseases.

Provided are modified microorganisms, such as live recombinant commensal bacteria, that express a heterologous antigen, and methods of using the modified microorganisms to induce an antigen-specific immune response to the heterologous antigen. The modified microorganism can be used to induce a regulatory T cell immune response to the heterologous antigen to treat an autoimmune disease in a subject in need thereof, or can be used to induce an effector T cell immune response to the heterologous antigen to treat a proliferative disease in a subject in need thereof.

The disclosure provides compositions comprising at least one assembly comprising a peptide and a major histocompatibility complex (MHC), wherein the peptide is an integral component of the MHC, wherein the peptide is attached to a surface at its C-terminus through a linker and wherein the peptide is synthesized on the surface. In certain embodiments, the compositions comprise a plurality of assemblies in a spatially-ordered array. The disclosure provides methods for making and using these compositions.

The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

The present disclosure relates to fusion proteins that comprise one or more modified alpha virus surface glycoproteins and one or more tumor specific antigens. Also disclosed are fusion proteins that comprise one or more modified alpha virus surface glycoproteins and one or more viral specific antigens. Also disclosed are fusion proteins that comprise one or more modified alpha virus surface glycoproteins. It also relates to methods to activate the immune system in cancer patients to infiltrate and kill tumor cells or cells infected with a latent virus. The present disclosure provides a platform technology that elicits a faster, broader and stronger immune response using the fusion proteins.

Disclosed are immunotherapeutic compositions and the concurrent use of combinations of such compositions for the improved induction of therapeutic immune responses and/or for the prevention, amelioration and/or treatment of disease, including, but not limited to, cancer and infectious disease.