The present invention relates to novel B7H6/CD3 binding proteins. The invention also relates to nucleic acids encoding such proteins; to methods for preparing such proteins; to host cells expressing or capable of expressing such proteins; to compositions comprising such proteins; and to uses of such proteins or such compositions, in particular for therapeutic purposes in the field of cancer diseases.

The present invention concerns a thermosensitive polymeric hydrogel comprising at least one thermosensitive copolymer, one aqueous solution, and a mucoadhesive excipient, wherein said thermosensitive polymeric hydrogel further comprises at least one immunostimulatory adjuvant and/or at least one cytokine and/or at least one chemokine and/or atleast one heat shockprotein. Another object of the invention is a thermosensitive polymeric hydrogel according to the invention for use in the treatment of tumors or metastasis in a subject having a cancer, preferably a metastatic cancer.

The present disclosure provides an allogeneic whole cell cancer vaccine platform that includes compositions and methods for treating and preventing breast cancer. Provided herein are compositions containing a therapeutically effective amount of cells from one or more cancer cell lines, some or all of which are modified to (i) inhibit or reduce expression of one or more immunosuppressive factors by the cells, and/or (ii) express or increase expression of one or more immunostimulatory factors by the cells, and/or (iii) express or increase expression of one or more tumor-associated antigens (TAAs), including TAAs that have been mutated, and which comprise cancer cell lines that natively express a heterogeneity of tumor associated antigens and/or neoantigens, and/or (iv) express one or more tumor fitness advantage mutations, including but not limited to driver mutations. Also provided herein are methods of making and preparing the breast cancer vaccine compositions and methods of use thereof.

The present application is related to a method of treating a cancer by administering to a human subject multiple doses of a mRNA cancer vaccine formulated as a lipid nanoparticle wherein the cancer vaccine comprises one or more mRNAs each having one or more open reading frames encoding 3-50 peptide epitopes, and wherein each of the peptide epitopes are portions of personalized cancer antigens or portions of cancer hotspot antigens. The present application further relates to a method of treating cancer by combining anti-cancer immunotherapy with the administration of the aforementioned mRNA cancer vaccine.

The invention provides improved strategies, prognostic indicators, compositions, and methods for producing personalized neoplasia vaccines. More particularly, embodiments of the present disclosure relate to the identification of neoplasia-specific neo-epitopes to predict survival and to identify and design subject-specific neo-epitopes, further assessing the identified neo-epitopes encoded by said mutations to identify neo-epitopes that are known or determined, or predicted to engage regulatory T cells and/or other detrimental T cells (including T cells with potential host cross-reactivity and/or anergic T cells), and excluding such neo-epitopes that are known, determined, or predicted) to engage regulatory T cells and/or other detrimental T cells (including T cells with potential host cross-reactivity and/or anergic T cells) from the subject-specific neo-epitopes that are to be used in personalized neoplasia vaccines. The present disclosure further relates to a novel ranking system for determining the optimal subject-specific neo-epitopes that are to be used in personalized neoplasia vaccines.

Provided are immunostimulatory bacteria with genomes that are modified to, for example, reduce toxicity and improve the anti-tumor activity, such as by increasing accumulation in the tumor microenvironment, particularly in tumor-resident myeloid cells, improving resistance to complement inactivation, reducing immune cell death, promoting adaptive immunity, and enhancing T-cell function. Also provided are immunostimulatory bacteria for use as vaccines, and for delivery of mRNA. The immunostimulatory bacterium comprise genome modifications resulting in an increase in colonization of phagocytic cells, which delivers encoded therapeutic products to phagocytic cells, and permits, among other routes, systemic administration of the immunostimulatory bacteria. The increase in colonization of phagocytic cells also provides for use of immunostimulatory bacteria for direct tissue administration for use as vaccines.

Use of an IL-Iβ binding antibody or a functional fragment thereof, especially canakinumab or a functional fragment thereof, or gevokizumab or a functional fragment thereof, and biomarkers for the treatment of cancer with at least partial inflammatory basis, e.g., CML.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The present disclosure provides a composition for preventing or treating a benign tumor. Provided is a composition for preventing or treating a benign tumor that comprises a WT1 peptide or an analog thereof, or a nucleic acid molecule encoding a WT1 peptide or an analog thereof. In a specific embodiment, the present disclosure provides a composition for preventing or treating a benign tumor that comprises a WT1 peptide or an analog thereof, or a nucleic acid molecule encoding a WT1 peptide or an analog thereof. In a preferred embodiment, the composition for preventing or treating a benign tumor (e.g. familial adenomatous polyposis) according to the present disclosure comprises a killer type WT1 peptide and/or a helper type WT1 peptide. In a further preferred embodiment, the WT1 peptide is WT1.sub.126 killer peptide and/or WT1.sub.35 helper peptide. In another aspect, provided are a method of inducing WT1 peptide-specific CTLs, a method of inducing WT1-specific helper T cells, and a method of inducing dendritic cells presenting a WT1 peptide.

The present disclosure provides compositions and methods of eliciting an anti-tumor immune response and treating cancer comprising at least one peptide of KRAS.