The present disclosure provides a recombinant oncolytic myxoma vims engineered to express a soluble form of an immune checkpoint protein in conjunction with a cytokine/chemokine and/or a tumor antigen. In certain aspects, the oncolytic myxoma virus is a replication competent virus such as myxoma vims. Methods of cancer treatment comprising administering the recombinant oncolytic myxoma virus expressing the soluble form of the immune checkpoint protein are also provided.

A microparticle is described comprising an antigen and a costimulatory component derived from an antigen presenting cell. The microparticle may be used for stimulating T cells ex vivo, followed by administration to a subject, e.g., as part of a personalized, customized therapeutic treatment of cancer or a tumor, an autoimmune disease or an allergic reaction, hypersensitivity reaction, an infection or infectious disease, an injury or other damage, a transplant or other surgical site, or a blood clot. It may also be used for the controlled release of a cytokine for the regulation of immunity in general and for other therapeutic uses. Methods of treating a disease or medical condition in a subject by exposing leukocytes from the subject to the microparticle, then reinfusing the leukocytes into the subject are provided. Methods of preparing an activated cytotoxic T cell population specific for an antigen are also provided.

The invention covers the use of certain classes of lipids including cationic lipids in ex-vivo dendritic cell therapies. The cationic lipids enhance antigen uptake, processing and presentation of the processed antigens by dendritic cells to CD8+ and CD4+ T-cells via the MHC classes I and II presentation pathways respectively. Antigen uptake via cationic lipid by dendritic cells result in significant lowering of the population of the immune suppressive regulatory T cells in the tumors and a significant increase of the tumor targeting cytotoxic T-cells. Loss of regulatory T cells and increase of tumor specific cytotoxic cells are conducive to effective elimination of the tumors.

The present disclosure relates to methods and agents for antigen vaccination and inducing effective antigen-specific immune effector cell responses such as T cell responses. Specifically, the present disclosure relates to methods comprising administering to a subject (i) non-immunogenic RNA encoding a peptide or protein comprising an epitope for inducing an immune response against an antigen in the subject, i.e., non-immunogenic RNA encoding vaccine antigen; and (ii) an immunostimulant or RNA encoding an immunostimulant. Administering to the subject non-immunogenic RNA encoding vaccine antigen may provide (following expression of the RNA by appropriate target cells) vaccine antigen for stimulation, priming and/or expansion of immune effector cells and, thus, may induce an immune response against vaccine antigen (and disease-associated antigen) in the subject.

The present invention relates to an immunomodulator, and in particular to a chemokine-5 like agent with activities with a range of chemokine receptors. The invention relates to the use of this chemokine-like agent and variants thereof as a medicament.

Multi-epitope, pan-coronavirus recombinant vaccine compositions featuring a combination of highly conserved B cell epitopes, highly conserved CD4+ T cell epitopes, and highly conserved CD8+ T cell epitopes, at least one of which is derived from a non-spike protein. The present invention uses several immuno-informatics and sequence alignment approaches and multiple immunological assays in vitro using human blood and saliva samples from COVID patients and healthy patients to identify several human B cells, CD4+ and CD8+ T cell epitopes that are highly conserved and antigenic in vitro. The Invention also used an in vivo unique mouse model of ACE2/HLA-A0201/HLA-DR triple transgenic mouse model to test the immunogenicity and the protective efficacy against SARS-CoV-2 infection and COVID-Like symptoms, of the identified B and T cell epitopes and of the resulting multi-epitope-pan-Coronavirus vaccine candidates. The vaccine compositions herein have the potential to provide long-lasting B and T cell immunity regardless of Coronaviruses mutations.

In one aspect, the present invention provides a method for treating cancer comprising tumor cell vaccination in combination with hematopoietic and immune cell transplantation. In some embodiments, the method involves autologous tumor cell vaccination prior to autologous hematopoietic and immune cell transplantation. In another aspect, the present invention provides a method of purifying tumor cells from a subject in preparation for vaccination.

The present invention provides a chimeric cytokine receptor (CCR) comprising: (i) an exodomain which binds to a ligand selected from a tumour secreted factor, a chemokinc and a cell-surface antigen; and (ii) a cytokine receptor cndodomain.

The invention described herein relates to methods for treating a patient having a plurality of HLA-negative cancer cells or cancer cells with reduced HLA expression with IFN-alpha in an amount sufficient to expand and/or activate immune cells such that the activated and/or expanded immune cells kill one or more of HLA-negative cancer cells or the cancer cells with reduced HLA expression.

This invention provides compositions and methods for cryoprotection of recombinant live cancer cells. Specifically, an improved cryoprotective medium is provided which includes a hydroxyethyl starch and/or derivative thereof alone or in combination with either DMSO or glycerol.