Provided herein are recombinant polynucleotides including a first nucleic acid sequence encoding an antigen, and a second nucleic acid sequence encoding an enzyme of an amino acid catabolic pathway. The provided recombinant polynucleotides are particularly useful for inducing long-lived immune responses having improved memory characteristics. Also provided are pharmaceutical compositions, viral particles, and host cells including the disclosed recombinant polynucleotides, and methods for using the disclosed materials.

The invention relates to prophylaxis and therapy of cancer. In particular there is provided a protein Tryptophan2,3-di-oxygenase (TDO) or peptide fragments here of that are capable of eliciting anti-cancer immune responses. Specifically, the invention relates to the use of TDO or peptides derived thereof or TDO specific T-cells for treatment of cancer. The invention thus relates to an anti-cancer vaccine which optionally may be used in combination with other immunotherapies and to TDO specific T-cells adoptively transferred or induced in vivo by vaccination as a treatment of cancer. It is an aspect of the invention that the medicaments herein provided may be used in combination with cancer chemotherapy treatment. A further aspect relates to the prophylaxis and therapy of infections by the same means as described above.

A mutated tryptophan oxidase suitable for practical implementation is described herein. Specifically, a mutated tryptophan oxidase wherein at least one amino acid residue of a wild-type tryptophan oxidase is mutated and, as a result, has higher tryptophan oxidase activity and/or stability as compared to the wild-type tryptophan oxidase. The mutated tryptophan oxidase can be derived from a wild-type tryptophan oxidase having at least one of Motifs (2), (3), (5), (7), (9), (11), (13), and (14), and at least one amino acid residue in any of these motifs can have mutation. The mutated tryptophan oxidase also can have a mutation of one or more amino acid residues in an amino acid sequence represented by SEQ ID NO: 2 and a sequence homologous thereto.

The invention relates to prophylaxis and therapy of cancer. In particular there is provided a protein Tryptophan 2,3-dioxygenase (TDO) or peptide fragments here of that are capable of eliciting anti-cancer immune responses. Specifically, the invention relates to the use of TDO or peptides derived thereof or TDO specific T-cells for treatment of cancer. The invention thus relates to an anti-cancer vaccine which optionally may be used in combination with other immunotherapies and to TDO specific T-cells adoptively transferred or induced in vivo by vaccination as a treatment of cancer. It is an aspect of the invention that the medicaments herein provided may be used in combination with cancer chemotherapy treatment. A further aspect relates to the prophylaxis and therapy of infections by the same means as described above.

The invention relates to prophylaxis and therapy of cancer. In particular there is provided a protein Tryptophan 2,3-dioxygenase (TDO) or peptide fragments here of that are capable of eliciting anti-cancer immune responses. Specifically, the invention relates to the use of TDO or peptides derived thereof or TDO specific T-cells for treatment of cancer. The invention thus relates to an anti-cancer vaccine which optionally may be used in combination with other immunotherapies and to TDO specific T-cells adoptively transferred or induced in vivo by vaccination as a treatment of cancer. It is an aspect of the invention that the medicaments herein provided may be used in combination with cancer chemotherapy treatment. A further aspect relates to the prophylaxis and therapy of infections by the same means as described above.

Provided are methods of treatment involving immunotherapy, such as T cell therapy, and administration of a tryptophan metabolism and/or kynurenine pathway modulator. In some embodiments, the method includes a combination therapy that involves administration of engineered T cells, such as chimeric antigen receptor (CAR)-expressing cells, and a tryptophan metabolism and/or kynurenine pathway modulator, such as an inhibitor of an enzyme. Also provided are engineered cells in which the expression of a molecule involved in the kynurenine pathway is modified. Also provided are methods of manufacturing engineered cells, cells, compositions, methods of administration to subjects, nucleic acids and kits for use in the methods. In some aspects, features of the methods and cells provide for increased or improved activity, activity, outcome, function, response, persistence, expansion and/or proliferation of cells for adoptive cell therapy.

Provided are methods of treatment involving immunotherapy, such as T cell therapy, and administration of a tryptophan metabolism and/or kynurenine pathway modulator. In some embodiments, the method includes a combination therapy that involves administration of engineered T cells, such as chimeric antigen receptor (CAR)-expressing cells, and a tryptophan metabolism and/or kynurenine pathway modulator, such as an inhibitor of an enzyme. Also provided are engineered cells in which the expression of a molecule involved in the kynurenine pathway is modified. Also provided are methods of manufacturing engineered cells, cells, compositions, methods of administration to subjects, nucleic acids and kits for use in the methods. In some aspects, features of the methods and cells provide for increased or improved activity, activity, outcome, function, response, persistence, expansion and/or proliferation of cells for adoptive cell therapy.

A system and a method for identifying novel hIDO inhibitors.

A nanoplatform assembly for detection of arginase, indoleamine 2,3-dioxygenase 1, and/or tryptophan 2,3-dioxygenase. The nanoplatform comprises an oligopeptide, which is used as a linker between two particles. More preferably, the linker is comprised of an oligopeptide containing a substrate for the target enzyme, where the substrate is chemically or physically modified by the target enzyme (but not cleaved). A central particle with a plurality of oligopeptide-tethered detectable particles and a plurality of directly attached detectable particles is described. Posttranslational modification of the oligopeptide leads to changes in the detectable signals from the first and/or second particles in the nanoplatform, which can be correlated to enzyme activity and concentration.

A mutated tryptophan oxidase suitable for practical implementation is described herein. Specifically, a mutated tryptophan oxidase wherein at least one amino acid residue of a wild-type tryptophan oxidase is mutated and, as a result, has higher tryptophan oxidase activity and/or stability as compared to the wild-type tryptophan oxidase. The mutated tryptophan oxidase can be derived from a wild-type tryptophan oxidase having at least one of Motifs (2), (3), (5), (7), (9), (11), (13), and (14), and at least one amino acid residue in any of these motifs can have mutation. The mutated tryptophan oxidase also can have a mutation of one or more amino acid residues in an amino acid sequence represented by SEQ ID NO: 2 and a sequence homologous thereto.