The present disclosure provides a Farmington virus formulated to induce an immune response in a mammal against a tumour associated antigen. The Farmington virus may express an antigenic protein that includes an epitope from the tumour associated antigen. The Farmington virus may be formulated in a composition where the virus is separate from an antigenic protein that includes an epitope from the tumour associated antigen. The present disclosure also provides a prime:boost therapy for use in inducing an immune response in a mammal. The boost includes a Farmington virus, or a composition that includes a Farmington virus.

The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or in B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at least one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

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 relates to RNA, particularly an immunostimulatory RNA (isRNA), a coding RNA or a combination thereof, for use in the treatment or prophylaxis of a disease, in particular a tumor and/or cancer disease. The present invention also provides pharmaceutical compositions, and a kit comprising the RNA(s). Further, the invention also comprises medical uses of the RNA(s) and compositions comprising the RNA(s).

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.

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.

The present invention provides methods of treating, preventing or delaying the progress of cancer and/or tumour in a subject comprising administering to the subject a treatment regimen comprising an effective amount of a PD-1 axis binding antagonist and a population of modified immunoresponsive cells expressing or presenting a heterologous TCR. The invention also provides methods of enhancing immune function in a subject having cancer and/or tumour comprising administering to the subject a treatment regimen comprising an effective amount of a PD-1 axis binding antagonist and a population of modified immunoresponsive cells expressing or presenting a heterologous TCR.

The present invention provides methods of treating, preventing or delaying the progress of cancer and/or tumour in a subject comprising administering to the subject a treatment regimen comprising an effective amount of a PD-1 axis binding antagonist and a population of modified immunoresponsive cells expressing or presenting a heterologous TCR. The invention also provides methods of enhancing immune function in a subject having cancer and/or tumour comprising administering to the subject a treatment regimen comprising an effective amount of a PD-1 axis binding antagonist and a population of modified immunoresponsive cells expressing or presenting a heterologous TCR.