Methods and compositions are provided related to therapeutic receptors, including chimeric antigen receptors (CARs), capable of specifically binding TYRP-1. The disclosed compositions include, for example, cells (e.g., immune cells) expressing TYRP-1 specific CARs, nucleic acids encoding TYRP-1 specific CARs, and TYRP-1 specific CAR polypeptides. Certain aspects relate to methods of treating cancer, including melanoma, using compositions comprising TYRP-1 specific CARs, for example cells expressing TYRP-1 specific CARs. In some embodiments, provided herein are chimeric polypeptides comprising a TYRP-1 binding domain, a hinge region, a transmembrane domain, and an intracellular signaling domain.

The present invention provides an in vitro method for the manufacture of a dendritic cell (DC) cancer vaccine, said method comprising the steps of: (i) providing a plurality of phagocytosable particles, wherein each phagocytosable particle comprises a core and an antigenic construct tightly associated to the core, wherein the antigenic construct comprises at least one epitope peptide having an amino acid sequence corresponding to an amino acid sequence of a part of a protein or peptide known or suspected to be expressed by a cancer cell in a subject; (ii) providing a sample of DCs; and (iii) contacting the sample of DCs with the plurality of phagocytosable particles in vitro and under conditions allowing for the phagocytosis of at least one phagocytosable particle by a DC. The present invention also provides a DC cancer vaccine produced by the method of the invention, and the use a DC cancer vaccine of the invention as a medicament and for the ex vivo expansion of anticancer T-cells.

The present disclosure is directed to compositions and methods of treating Triple Negative Breast Cancer (TNBC) in a human subject. A method of treating TNBC in a human subject includes administering a therapeutically effective amount of a neoantigen vaccine composition comprising a fusion protein comprising at least one TNBC-associated neoantigen epitope joined to a mutant ubiquitin protein, or a nucleic acid molecule encoding such a protein.

The present invention provides a method for treating a disease in a subject, which comprises the step of administering to the subject a plurality of cells which express: (a) a chimeric antigen receptor (CAR); and (b) a mutant version of calcineurin A and/or calcineurin B which is resistant to the calcineurin inhibitor. The subject may be receiving or have received treatment with a calcineurin inhibitor. The CAR-expressing cells may be administered prior to, following, simultaneously with or in combination with a calcineurin inhibitor.

The present disclosure provides signal transducer and activator of transcription (STAT)-activated macrophages, compositions comprising STAT-activated macrophages, methods of making STAT-activated macrophages, and methods of treating diseases, e.g., cancer, by administering a therapeutically effective amount of STAT-activated macrophages.

Disclosed are invariant natural killer T (iNKT) cells engineered using hematopoietic stem and progenitor cells (HSPCs) and methods of making and using thereof. Specifically, the engineered cells iNKT are genetically modified to contain at least one exogenous invariant natural killer T cell receptor (iNKT TCR) nucleic acid molecule. Further disclosed are iNKT TCR nucleotide sequences and codon optimized sequences for expression.

An object is to provide a PRAM-binding molecule. This object is achieved by a PRAM-binding molecule comprising a heavy-chain variable region containing a heavy-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO: 1, a heavy-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO: 2, and a heavy-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO: 3, and/or a light-chain variable region containing a light-chain CDR1 comprising the amino acid sequence represented by SEQ ID NO: 9, a light-chain CDR2 comprising the amino acid sequence represented by SEQ ID NO: 10, and a light-chain CDR3 comprising the amino acid sequence represented by SEQ ID NO: 11.

The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

There is described herein a method for improving the anti-cancer properties of T-cells, the method comprising: providing a population of T-cells; and culturing the T-cells in an environment that activates the GCN2 pathway.

The present invention provides an immune effector cell that comprises a chimeric antigen receptor (CAR) specific for a tag of a tagged polypeptide, wherein said polypeptide binds to an antigen of a target cell, and a chimeric costimulatory receptor (CCR) specific for a further antigen. The CCR is not able to mediate said immune response on its own but boosts the immune response of said immune effector cell triggered by the CAR.