Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer.

An OCTS-based CAR-T vector for treating pancreatic cancer and malignant mesothelioma includes lentiviral skeleton plasmid, human EF1α promoter (SEQ ID NO: 14), OCTS chimeric receptor structural domain, and PDL1 single-chain antibody; the OCTS chimeric receptor structural domain consists of CD8 leader chimeric receptor signal peptide (SEQ ID NO: 15), PDL1 single-chain antibody light chain VL (SEQ ID NO: 16), PDL1 single-chain antibody heavy chain VH (SEQ ID NO: 17), mesothelin single-chain antibody light chain VL (SEQ ID NO: 18), mesothelin single-chain antibody heavy chain VH (SEQ ID NO: 19), antibody Inner-Linker (SEQ ID NO: 20), single-chain antibody Inter-Linker (SEQ ID NO: 21), CD8 Hinge chimeric receptor linker (SEQ ID NO: 22), CD8 Transmembrane chimeric receptor transmembrane domain (SEQ ID NO: 23), TCR chimeric receptor T cell activation domain (SEQ ID NO: 26) and chimeric receptor co-stimulator domain.

The present invention is the use of designed recombinant viruses for the treatment of various forms of malignant tumors. The recombinant viruses of the invention are those in which one or more regions of the wild type virus was exchanged with a synthetic recoded sequence that reduces the codon pair score relative to human codon pair bias, or that increase the number for CpG di-nucleotides, or that increases the number of UpA di-nucleotides. The method of the present invention is particularly useful for the treatment of malignant tumors in various organs, such as: breast, skin, colon, bronchial passage, epithelial lining of the gastrointestinal, upper respiratory and genito-urinary tracts, liver, prostate and the brain. Astounding remissions in experimental animals have been demonstrated for the treatment of malignant glioblastoma multiforme, as well as for the treatment of breast cancer and melanoma as well.

A chimeric antigen receptor targeting to human NKG2DL, its encoding sequence, and its modified immune response cells, and the preparation and application thereof are provided. This invention constructs a chimeric antigen receptor targeting to NKG2DL and its modified immune response cell based on the NKG2D molecule. The amino acid sequence of the chimeric antigen receptor targeting the human NKG2DL is sequentially connected by the following amino acid sequences from an amino terminal to a carboxy terminal: an amino acid sequence of a guiding sequence, an amino acid sequence of human NKG2D, an amino acid sequence of a human CD8 hinge region, an amino acid sequence of a human CD8 transmembrane region, an amino acid sequence of a human 4-1BB intracellular domain and an amino acid sequence of a human CD3 zeta domain.

T cells, notably CD8 T cells, are known to be essential players in tumor eradication as the presence of tumor-infiltrating lymphocytes (TILS) in several cancers positively correlates with a good prognosis. To eliminate tumor cells, CD8 T cells recognize tumor antigens, which are MHC I-associated peptides present at the surface of tumor cells, with no or very low expression on normal cells. Described herein a proteogenomic approach using RNA-sequencing data from cancer and normal-matched mTEC.sup.hi samples in order to identify non-tolerogenic tumor-specific antigens derived from (i) coding and non-coding regions of the genome, (ii) non-synonymous single-base mutations or short insertion/deletions and more complex rearrangements as well as (iii) endogenous retroelements, which works regardless of the sample's mutational load or complexity.

The present disclosure relates, inter alia, to compositions and methods for treating cancer, including lung cancer (e.g., Non-Small Cell Lung Cancer), comprising administering (a) a cell harboring an expression vector comprising a nucleotide sequence that encodes a secretable vaccine protein and (b) an immune checkpoint inhibitor to a subject in need thereof.

Disclosed in the present invention are antibodies to programmed death ligand (PD-L1) and an application thereof, and in particular, an application thereof in treating and/or preventing PD-L1 related conditions.

The present invention provides a peptide comprising, consisting essentially of or consisting of (i) the amino acid sequence KMPEAGEEQPQV (SEQ ID NO: 1); (ii) the amino acid sequence ISQTPGINL (SEQ ID NO: 2); or (iii) the amino acid sequence of SEQ ID NO: 1 or 2 with the exception of 1, 2 or 3 amino acid substitutions and/or 1, 2 or 3 amino acid insertions, and/or 1, 2 or 3 amino acid deletions, wherein the peptide forms a complex with a Major Histocompatibility Complex (MHC) molecule. Also provided are a complex of the peptide a Major Histocompatibility Complex (MHC) molecule, a nucleic acid molecule comprising a nucleic acid sequence encoding the peptide, a vector comprising such a nucleic acid sequence, a cell comprising such a vector and a binding moiety that binds the peptide.

Provided herein are methods and compositions related to bacteria of genus Burkholderia useful as therapeutic agents.

Methods of expanding tumor infiltrating lymphocytes (TILs) in the presence of an adenosine A2A receptor (A2aR) antagonist, such as vipadenant, CPI-444 (ciforadenant), SCH58261, SYN115, ZM241385, SCH420814, a xanthine superfamily A2aR antagonist, or related adenosine receptor 2A antagonist, and uses of expanded TILs in the treatment of diseases such as cancer are disclosed herein. In addition, therapeutic combinations of TILs and A2aR antagonists, including compositions and uses thereof in the treatment of diseases such as cancer are disclosed herein.