The present disclosure provides populations of cells comprising partially mature and optimally activated dendritic cells that can be used for administration to individuals having a cancer and/or tumor. Partially matured dendritic cells, those contacted with a dendritic cell maturation agent for about 10 to about 19 hours, upon administration efficiently take up and process tumor antigens in the area of the tumor site, complete maturation, and can subsequently migrate to the lymph nodes of a treated individual. Once in a lymph node the now fully mature antigen presenting dendritic cells secrete the appropriate cytokines (e.g., TNFa, IL-6, IL-8, and/or IL-12) and contact T cells inducing a substantial and optimal clinical and/or anti-tumor immune response.

The present disclosure relates to a genetically modified dendritic cell or precursor thereof expressing at least one anti-gen-derived peptide and at least one immuno-modulatory molecule, its medical use and method of preparation. The invention also relates to an in vitro method to produce IL-10-producing CD49b+LAG-3+ Tr1 cells or antigen-specific FOXP3+ T cells and relative medical uses and pharmaceutical compositions.

The invention concerns APCs, such as DCs, comprising a combination of an exogenous type I interferon and an exogenous CD40-L or one or more heterologous nucleic acid sequences encoding a combination of an exogenous type I IFN and an exogenous CD40-L, such as a combination of IFNβ and CD40-L; and methods for treating a malignancy by administering such APCs to a subject in need thereof. In certain embodiments, a subject is treated with an irradiation therapy before administering the APCs, such as DCs, of the invention. The invention also concerns an oncolytic virus comprising a combination of a type I IFN and CD40-L or one or more nucleic acid sequences encoding a combination of a type I IFN and CD40-L, such as a combination of IFNβ and CD40-L; and methods for treating a malignancy by administering such oncolytic virus to a subject in need thereof.

Methods and compositions for identifying tumor antigens of human lymphocytes, and for treating subjects having cancer, are provided herein.

Dendritic cells containing tumor lysate loaded particles are prepared. The dendritic cells present tumor antigens to elicit the Major Histocompatibility Complex class I pathway and can be used as a vaccine to treat cancer, including ocular melanoma.

Disclosed herein is a different and novel approach to cancer vaccines using a subject's own dendritic cells (DCs) and macrophages (Mphs) in combination to present cancer antigens to the immune system. Further disclosed are methods of producing monocyte-derived autologous DCs and Mphs loaded ex vivo with particular whole irradiated cancer cells which generates optimally activated immunostimulatory antigen-presenting cells (APCs) as a superior method for stimulating robust and long-lasting immunity to a particular cancer in vivo as compared with more traditional vaccination methods. Compositions, methods of use and methods for preparation of these DCs and Mphs with cancer cells are also disclosed herein.

Described herein are compositions and methods for treating cancer through the combination of tumor antigen-pulsed dendritic cells and Dengue Virus. The combination of the two forms of therapeutic intervention provides enhanced tumor cell reduction compared to either alone. The cancer targeted by compositions and methods described herein may be a solid cancer or blood cancer.

Provided methods of obtaining a plurality of T cell receptors specifically recognizing a target tumor antigen peptide from an individual that has clinically benefitted from an immunotherapy, such as Multiple Antigen Specific Cell Therapy. Also provided tumor-specific TCRs, engineered immune cells expressing the TCRs and methods of treating a disease using the engineered immune cells.

The present disclosure provides methods of increasing sensitivity of a tumor to treatment with an immune checkpoint inhibitor (ICI) in a subject and methods of treating a subject with an immune checkpoint inhibitor (ICI)-resistant tumor. The methods comprise administering to the subject a composition comprising a liposome comprising a cationic lipid and mRNA molecules, wherein the liposome is systemically administered to the subject. Also provided are methods of increasing the number of activated plasmacytoid dendritic cells (pDCs) in a subject in need thereof, comprising administering to the subject a composition comprising a liposome comprising a cationic lipid and mRNA molecules, wherein the liposome is systemically administered to the subject. Combination therapy with anti-PD-L1 mAb. Related methods of treatment and methods of preparing a dendritic cell vaccine are additionally provided.

The invention is in the field of medical sciences. It provides means and methods for the treatment of cancer. More in particular, it provides cells and cell lines that can be developed into fully functional dendritic cells. These cells endogenously express cancer-specific antigens, which makes them particularly suited for the treatment of different kinds of cancer. More in particular, the invention relates to a precursor cell line for dendritic cells called DC-One as deposited at the DSMZ under accession number DSMZ ACC3189 on Nov. 15, 2012.