The present disclosure relates to methods and compositions comprising derivatized-chitosan polyplexes reversibly coated with a polyanion-containing block co-polymer for the localized expression of IL-12 in mucosal tissues, preferably in combination with an IFN-1 activator/inducer, for use in cancer immunotherapy.

Compositions for stabilizing and delivering proteins and/or other bioactive agents are disclosed. The bioactive agents are embedded or encapsulated in a crystalline matrix. Typically the bioactive agents are in the form of micro- or nanoparticles. The crystalline matrix confers enhanced stability to the agents embedded therein relative to other microparticulate or nanoparticulate bioactive agents. The carriers are especially useful for stabilizing bioactive macromolecules, such as proteins.

Disclosed herein is an oncolytic recombinant Maraba virus whose genome comprises one or more nucleic acid sequences that, in combination, encode an interleukin-12 (IL12) protein or a functional portion thereof. A method for treating a cancer in a patient using the oncolytic recombinant Maraba virus is also disclosed. The present disclosure also provides a tumour cell infected with an oncolytic rhabdovirus whose genome comprises one or more nucleic acid sequences that, in combination, encode an interleukin-12 (IL12) protein or a functional portion thereof, for use as an infected cell vaccine (ICV) for the treatment of a cancer. A method for treating a cancer in a patient using the infected cell vaccine is also disclosed.

The present application relates to novel prodrugs of IL-12. Further included in the present application are methods of making and using the novel prodrugs.

The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of combinations of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide or an interleukin 36γ (IL-36-gamma) polypeptide), and an immune response co-stimulatory signal polypeptide (e.g., an OX40L polypeptide).

The present disclosure relates to polynucleotides comprising an open reading frame of linked nucleosides encoding human interleukin-12 (IL12), functional fragments thereof, and fusion proteins comprising IL12. In some embodiments, the open reading frame is sequence-optimized. In particular embodiments, the disclosure provides sequence-optimized polynucleotides comprising nucleotides encoding the polypeptide sequence of human IL12, or sequences having high sequence identity with those sequence optimized polynucleotides.

Provided are methods for treating a disease using bioengineered enucleated cells. Also provided herein are compositions comprising enucleated cells, wherein the enucleated cells have been loaded with clinically relevant biomolecules.

A method of eliciting an immune response in a patient who has a cancer includes administering to said patient a composition containing a population of activated T cells that selectively recognize the cancer cells in the patient that aberrantly express a peptide consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303), in which the peptide is in a complex with an MHC molecule.

A method of eliciting an immune response in a patient who has a cancer includes administering to said patient a composition containing a population of activated T cells that selectively recognize the cancer cells in the patient that aberrantly express a peptide consisting of the amino acid sequence of GVYDGEEHSV (SEQ ID NO: 303), in which the peptide is in a complex with an MHC molecule.

Provided is a composition for treating tumors in a subject comprising a therapeutically effective amount of an exosome carrying CTLA4-targeting miRNA and a therapeutically effective amount of an oncolytic herpes simplex virus expressing an immunostimulatory agent or both an immunostimulatory agent and an anti-PD-1 antibody. Wherein an exo-motif operably links to the seed sequence of the CTLA4-targeting miRNA to enhance the packaging of the CTLA4-targeting miRNA into the exosome.