T cell lymphoma mutations, compositions, and uses to enhance engineered t cell therapies

Abstract

The present disclosure relates generally to mutations in T cell lymphoma, and methods of use of the mutations in T cell therapy.

Description

Atty. Dkt. No.: 121384-0285T CELL LYMPHOMA MUTATIONS, COMPOSITIONS, AND USES TO ENHANCE ENGINEERED T CELL THERAPIESCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority to U.S. Provisional Application No. 63 / 695,341, filed September 16, 2024, the entire contents of which are incorporated herein by reference.STATEMENT OF GOVERNMENT SUPPORT

[0002] This invention was made with government support under grant number CA288003 awarded by the National Institutes of Health. The government has certain rights in the invention.FIELD

[0003] The present invention relates generally to T cell therapy. The disclosure provides vectors and engineered cells comprising polypeptides which enhance T cell persistence in cancer tells, the tumor microenvironment, and tumor draining lymph nodes. Also provided herein are methods for generating the engineered cells and therapeutic methods of use.BACKGROUND

[0004] The following description of the background of the present technology is provided simply as an aid in understanding the present technology and is not admitted to describe or constitute prior art to the present technology.

[0005] Adoptive and engineered T cell therapies, including chimeric antigen receptor (CAR) T cells, T cell receptor (TCR) engineered T cells, have emerged recently as important therapies for cancer, inflammation and infectious diseases. In adoptive cell therapy, infusions of T cells are used to recognize and eliminate tumor cells.

[0006] Current limitations in adoptive T cell therapy to treat cancer include fitness of T cells, persistence of T cells, and immunosuppressive environmental factors. Thus, the identification-1-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 and use of enhanced T cell therapies are needed for therapeutic purposes. This disclosure provides composition and methods that meet this need.SUMMARY

[0007] According to one embodiment, provided herein is a vector comprising a nucleic acid sequence encoding a polypeptide, the polypeptide comprising at least one T cell lymphoma wild-type or mutant protein or functional fragment thereof. In one aspect, the vector is selected from a plasmid, a herpes simplex virus, a retrovirus, an adenovirus, or an adeno- associated virus. In one aspect the retrovirus is a lentivirus.

[0008] According to another embodiment, provided herein is an engineered cell comprising a polypeptide or nucleotide encoding a polypeptide comprising at least one T cell lymphoma wild-type or mutant protein or functional fragment thereof.

[0009] In some aspects, the polypeptide of the vector or engineered cell comprises at least one selected from a FAS, FYN-TRAF3IP2, VAV1-STAP2, IL2RG, CTNNB1, CAPRIN- JAK2, mCTLA4-mCD28, IKZF2-ERBB4, PABPC1-TYK2, IL7R, mCD3E, TRAF3, IDH1, JAK3, RPL10, TLDC1, STAT3, DNMT3A, NFKB2, RASGRP1, AKT1, MAPK1, KHDRBS1-LCK, or VAV-MY01F mutant protein or functional fragment thereof, wherein the protein or functional fragment thereof is a variant of the wild-type protein. In some other aspects, the polypeptide comprises at least one selected from a AKT1, IL2RG, TBL1IR1, or IDH1 wild-type protein.

[0010] In one aspect, the vector is selected from a plasmid, a herpes simplex virus, a retrovirus, an adenovirus, or an adeno-associated virus. In one aspect the retrovirus is a lentivirus.

[0011] In one aspect the variant comprises a single-point, double-point, insertion, or fusion mutation of the wild-type protein. In one aspect the variant is in a B cell lymphoma mutation.

[0012] In one aspect, the engineered cell comprises the vector described herein.

[0013] In one aspect, the engineered cell is a T cell. In one aspect, the engineered cell comprises a receptor with specificity for a target antigen.-2-4927-7786-8905.2Atty. Dkt. No.: 121384-0285

[0014] In some embodiments, the polypeptide in the vector or engineered cell provided herein is selected from a variant presented in Tables 1 or 5. In some embodiments, the polypeptide in the vector or engineered cell is encoded by a sequence selected from SEQ ID NOs: 1-31.

[0015] In some embodiments, the variant is selected from: a FAS substitution at amino acid 265, a FYN-TRAF3IP2 fusion, a VAV1-STAP2 fusion, an IL2RG substitution at amino acid 315, a CTNNB1 substitution at amino acid 45, a CAPRIN-JAK2 fusion, a mCTLA4-mCD28 fusion, an IKZF2-ERBB4 fusion, a PABPC1-TYK2 fusion, an IL7R insertion of CPT between amino acids 244 and 245; an IL74 substitution at amino acid 7, a mCD3 substitution at amino acid 34, a TRAF3 substitution at amino acid 359, an IL2RG substitution at amino acid 315, an IDH1 substitution at amino acid 132, a JAK3 substitutions at amino acids 572, 589, or 583, an RPL10 substitution at amino acid 98, a TLDC1 substitution at amino acid 87, a STAT3 substitution at amino acid 618, a DNMT3A substitution at amino acid 882, a NFKB2 substitution at amino acid 882, a RASGRP1 substitution at amino acid 261, an AKT1 substitution at amino acid 17, a MAPK1 substitution at amino acid 321, a KHDRBS1-LCK Fusion, and / or a VAV1-MYO1F Fusion.

[0016] In one aspect, the engineered cell has increased or decreased signaling through the API, NF AT, NFKB, and / or PD1 pathways. In another aspect, the engineered cell has increased or decreased cytokine production. The cytokine can be selected from IL-2, IL-4, II- 5, TNF alpha, IFN- gamma and / or IL-13.

[0017] Also provided herein is a composition comprising the engineered cell and a pharmaceutically acceptable carrier.

[0018] Also provided herein are methods to increase the persistence of T cells in a cancer cell or tumor, comprising contacting the cancer cells or tumor with the engineered cell or composition described herein. In some aspects, the contacting is in vivo or in vitro.

[0019] Also provided herein are methods of treatment or therapeutic use in a subject in need thereof.-3-4927-7786-8905.2Atty. Dkt. No.: 121384-0285[00201 In one aspect, provided herein is a method to increase the persistence of T cells in a tumor microenvironment or tumor draining lymph nodes of a subject in need thereof, comprising administering to the subject in the engineered cell or composition described herein.[00211 In one aspect, provided herein is a method to prevent tumor recurrence in a subject in need thereof, comprising administering to the subject in the engineered cell or composition described herein after a subject has reduced tumor growth or symptoms. In one aspect the subject is in partial or complete remission.

[0022] In another aspect, provided herein is a to inhibit the growth of a cancer and / or increase the survival rate of a subject in need thereof, comprising administering to the subject in need the engineered cell or composition described herein.10023] In another aspect, provided herein is a method to inhibit the growth of a first cancer and / or increase the survival rate of a subject in need, comprising administering to the subject in need the engineered cell or composition, wherein growth of a second cancer is also inhibited after the first cancer is contacted with the engineered cell or composition, and wherein the first cancer comprises an antigen recognized by the engineered cell. The first cancer and the second cancer may be the same, related, or different. In one aspect, the second cancer is a metastasis of the first cancer. In one aspect, the first cancer is positive for a T-cell dependent antigen and the second cancer is negative for the T-cell dependent antigen.

[0024] In the methods of treatment described herein, the cancer, including the first and / or second cancer, may be a solid tumor. The cancer, including the first and / or second cancer, may be a small cell lung cancer, colorectal cancer, testicular cancer, ovarian cancer, melanoma, lymphoma, leukemia, multiple myeloma, prostate cancer, breast cancer, nonsmall cell lung cancer, gastric cancer, esophageal cancer, liver cancer, kidney cancer, head & neck cancer, glioblastoma, neuroblastoma, soft tissue sarcoma, uterine cancer, brain cancer, skin cancer, renal cancer, bladder cancer, pancreatic cancer, thyroid cancer, eye cancer, gastrointestinal cancer, carcinoma, or sarcoma.10025] In the methods of treatment described herein, the engineered cell or composition may be administered parenterally (including intramuscularly, subcutaneously, intradermally,-4-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 intravascularly, intravenously, intraarterially, intramedullary and intraihecally), intraperitoneally, or intratumorally. In the methods of treatment described herein, the subject in need may be a mammal, optionally a human.

[0026] According to one embodiment, provided herein is a method to generate a vector, comprising transferring a plasmid to a cell, wherein the plasmid comprises a nucleotide encoding a polypeptide comprising at least one T cell lymphoma wild-type protein or functional fragment thereof, or a T cell lymphoma protein mutant or functional fragment thereof. The nucleotide may have a sequence according one or more selected from SEQ ID NOs: 1-31. In some aspects, the vector is a retrovirus, optionally a lentivirus.

[0027] Kits containing the engineered cells and compositions described herein are also provided.BRIEF DESCRIPTION OF THE DRAWINGS

[0028] FIGURE 1 shows an exemplary T Cell Lymphoma Mutation Library. AA change indicates the specific mutation. For example, E17K indicates a substitution of E with K at amino acid 17. The variants follow conventional nomenclature of proteins, as taught for example in https: / / atlasgeneticsoncology.org / teaching / 30067 / nomenclature-for-the- description-of-mutations-and-other-sequence-variations, the entire contents of which are incorporated by reference.

[0029] FIGURE 2 shows the T Cell Lymphoma Mutation screening protocol.

[0030] FIGURE 3 shows the enrichment of library TILs compared to control OT-1 at Day 7 after T cell transfer. ****p<0.0001 unpaired t test. TIL is tumor-infiltrate lymphocytes. TILs are a measurement of persistence in the tumor on day 7 after T cell transfer.{0031 [ FIGURE 4 shows the PCL pooled log2 tumor fold change vs. rank. The screening of T Cell mutations show enrichment of known genes that enhance T Cell engraftment (ex.STAT5B) and depletion of genes known to negatively regulate T cell activation (PD-1). The higher log2fold change indicates increased persistence in the tumor.-5-4927-7786-8905.2Atty. Dkt. No.: 121384-0285[0032| FIGURE 5 shows the replicates of TCL mutant and wild-type protein screening. The two replicates shown together demonstrates reproducibility of the mutations to effect a change. The higher log2fold change indicates increased persistence in the tumor.

[0033] FIGURE 6 shows the T-cell accumulation in TIL and TdLN (tumor-draining lymph node) when tumors were treated with two TCL mutants, TRAF3 S359R and FOXP3 M370I. Mutations TRAF3 S359R and FOXP3 M370I found from TCL screening in vivo show significant accumulation in tumors and tumor draining lymph nodes compared to controls in dual transfer assay. Asterisks indicate significant. *** is significance at p<0.001 and * is significant at p<0.05.

[0034] FIGURE 7 shows a dual transfer competition assay in a B16-F10 / pmel. There was a 5-fold enrichment of fusion FYN-TRAF3IP2 expressing CD8 T cells compared to vector controls on Day 7.

[0035] FIGURES 8A-8C show that TCL mutants enhance CAR T cell signaling activation and IL2 production. (FIG. 8 A) shows the in vitro screen in CAR Jurkat Signaling cells. Mutations were introduced in Jurkat CAR T cells. Cells were cocultured with K562-CD19 target cells for 24 hours. IL2 secretion was measured by ELISA and T cell activation was measured by using fluorescent reporters for NFKB, API and NF AT. (FIG. 8B) shows increased IL-2 production in fusion FYN-TRAF3IP2 compared to the mcherry control. (FIG. 8C) shows altered signaling in AP1+, NFAT+, NFKB High, NFKB+, and PD1+ in T cells including mutation FYN-TRAF3IP2 or TRAF3.

[0036] FIGURE 9 shows a schematic of tumor challenge in mice.

[0037] FIGURES 10A-10E. (FIG. 10A). Schematic of timeline of tumor model. (FIG. 10B). Validation of CAPRIN-JAK2 in B16-F10 OVA models shows tumor clearance with treatment of IM CAPRIN-JAK2 expressing OT-1 CD8 T cells. (FIG. 10C). Peripheral tail vein sampling shows expansion of fusion cells in the blood in an antigen dependent manner. (FIG. 10D) Survival curves of mice treated with CAPRIN-JAK2. (FIG. 10E). Fold enrichment of CAPRIN-JAK2 TILs compared to OT-1 control Day 7 after T cell transfer. **** p<o 0001, **p<0.01 for two way ANOVA or unpaired t test.-6-4927-7786-8905.2Atty. Dkt. No.: 121384-0285[0038| FIGURES 11A-11H. (FIG. 11A). Schematic of timeline of tumor model. (FIG.11B). Validation of FYN-TRAF3IP2 in B16-F10 OVA models shows tumor clearance with treatment of IM FYN-TRAF3IP2 expressing OT-1 CD8 T cells. (FIG. 11C). Peripheral tail vein sampling shows expansion of fusion cells in the blood in an antigen dependent manner. (FIG. 11D). Survival curves of mice treated with FYN-TRAF3IP2. (FIG. HE). Fold enrichment of FYN-TRAF3IP2 TILs compared to OT-1 control Day 7 after T cell transfer. (FIG. HF). Weight change in control mice and treatment mice. (FIG. 11G). Validation of FYN-TRAF3IP2 in B16-F10 OVA models shows tumor clearance with treatment of 190k FYN-TRAF3IP2 expressing OT-1 CD8 T cells. Dashed lines show the individual animal and solid lines show the average. 2M and 190k refer to cell counts 2 million and 190 thousand, respectively. (FIG. 11H). Peripheral tail vein sampling shows expansion of fusion cells in the blood in an antigen dependent manner (individual mice).**p<0.01 for survival analysis, ***p<0.001 for unpaired t test.

[0039] FIGURES 12A-12C. (FIG. 12A). B 16-0 VA tumor rechallenge on contralateral flank at Day 60. (FIG. 12B). B16-F10 tumor rechallenge on Day 60. (FIG. 12C). Tail vein blood samples every 3-4 days after Day 60 double tumor rechallenge. **p<0.01 for two way ANOVA, ***p<0.001 for two way ANOVA.

[0040] FIGURES 13A-13C. (FIG. 13A). B16-OVA tumor rechallenge on contralateral flank at Day 305. (FIG. 13B). B16-F10 tumor rechallenge on Day 305 (FIG. 13C). Tail vein blood samples every 3-4 days after Day 305 double tumor rechallenge.

[0041] FIGURE 14 shows differential expression of cytokine genes in CD8+ T cells isolated from OT-I TCR transgenic mice and transduced with an MSCV retrovirus encoding genes listed in the figure.

[0042] FIGURE 15 shows differential expression of chemokines / chemokine receptor genes in CD8+ T cells isolated from OT-I TCR transgenic mice and transduced with an MSCV retrovirus encoding genes listed in the figure.

[0043] FIGURE 16 shows differential expression of cytokine genes in CD3+ T cells from healthy donors and transduced with lentivirus encoding genes listed in the figure.-7-4927-7786-8905.2Atty. Dkt. No.: 121384-0285

[0044] FIGURE 17 shows differential expression of chemokines / chemokine receptor genes in CD3+ T cells from healthy donors and transduced with lentivirus encoding genes listed in the figure.DETAILED DESCRIPTION

[0045] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the present application and relevant art and should not be interpreted in an idealized or overly formal sense unless expressly so defined herein. While not explicitly defined below, such terms should be interpreted according to their common meaning.

[0046] The terminology used in the description herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

[0047] Unless explicitly indicated otherwise, all specified embodiments, features, and terms intend to include both the recited embodiment, feature, or term and biological equivalents thereof.Definitions

[0048] Unless otherwise specified “a” or “an” means one or more.

[0049] All numeric values should be treated as having the term “about” placed before a specific numeric value.

[0050] As used herein, the term “about” placed before a specific numeric value may mean ±20% of the numeric value; ±18% of the numeric value, ±15% of the numeric value; ±12% of the numeric value; ±8% of the numeric value; ±5% of the numeric value; ±3% of the numeric value; ±2% of the numeric value; ±1% of the numeric value or ±0.5% of the numeric value.-8-4927-7786-8905.2Atty. Dkt. No.: 121384-0285

[0051] “Optional” or “optionally” means that the subsequently described circumstance may or may not occur, so that the description includes instances where the circumstance occurs and instances where it does not.

[0052] As used herein, “and / or” refers to and encompasses any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative (“or”).[ 00531 As used herein, the term “comprising” is intended to mean that the compounds, compositions and methods include the recited elements, but not exclude others. “Consisting essentially of’ when used to define compounds, compositions and methods, shall mean excluding other elements of any essential significance to the combination. Thus, a composition consisting essentially of the elements as defined herein would not exclude trace contaminants, e.g., from the isolation and purification method and pharmaceutically acceptable carriers, preservatives, and the like. “Consisting of’ shall mean excluding more than trace elements of other ingredients. Embodiments defined by each of these transition terms are within the scope of this technology.

[0054] In some embodiments, the term “engineered” or “recombinant” refers to having at least one modification not normally found in a naturally occurring protein, polypeptide, polynucleotide, strain, wild-type strain or the parental host strain of the referenced species. In some embodiments, the term “engineered” or “recombinant” refers to being synthetized by human intervention. As used herein, the term “recombinant protein” refers to a polypeptide which is produced by recombinant DNA techniques, wherein generally, DNA encoding the polypeptide is inserted into a suitable expression vector which is in turn used to transform a host cell to produce the heterologous protein.

[0055] The terms “polynucleotide”, “nucleic acid” and “oligonucleotide” are used interchangeably and refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides or analogs thereof. Polynucleotides can have any three dimensional structure and may perform any function, known or unknown. The following are non limiting examples of polynucleotides: a gene or gene fragment (for example, a probe, primer, EST or SAGE tag), exons, introns, messenger RNA (mRNA),-9-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 transfer RNA, ribosomal RNA, ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes and primers. A polynucleotide can comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs. If present, modifications to the nucleotide structure can be imparted before or after assembly of the polynucleotide. The sequence of nucleotides can be interrupted by non nucleotide components. A polynucleotide can be further modified after polymerization, such as by conjugation with a labeling component. The term also refers to both double and single stranded molecules. Unless otherwise specified or required, any embodiment of this disclosure that is a polynucleotide encompasses both the double stranded form and each of two complementary single stranded forms known or predicted to make up the double stranded form.

[0056] A polynucleotide is composed of a specific sequence of four nucleotide bases: adenine (A); cytosine (C); guanine (G); thymine (T); and uracil (U) for thymine when the polynucleotide is RNA. Thus, the term “polynucleotide sequence” is the alphabetical representation of a polynucleotide molecule. This alphabetical representation can be input into databases in a computer having a central processing unit and used for bioinformatics applications such as functional genomics and homology searching.

[0057] A “gene” refers to a polynucleotide containing at least one open reading frame (ORF) that is capable of encoding a particular polypeptide or protein after being transcribed and translated.

[0058] The term “express” refers to the production of a gene product, such as mRNA, peptides, polypeptides or proteins. As used herein, “expression” refers to the process by which polynucleotides are transcribed into mRNA or the process by which the transcribed mRNA is subsequently being translated into peptides, polypeptides, or proteins. If the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA in a eukaryotic cell.

[0059] As used herein, the term “overexpress” intends a level of expression of the mRNA, the protein or the polypeptide” that is greater than or exceeds the level of expression of the-10-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 mRNA, the protein or the polypeptide in a native, wild-type or cell that has not been engineered to increase expression.(0060] A “gene product” or alternatively a “gene expression product” refers to the amino acid (e.g., peptide or polypeptide) generated when a gene is transcribed and translated. In some embodiments, the gene product may refer to an mRNA or other RNA, such as an interfering RNA, generated when a gene is transcribed.[0061 | The term “encode” as it is applied to polynucleotides refers to a polynucleotide which is said to “encode” a polypeptide if, in its native state or when manipulated by methods well known to those skilled in the art, it can be transcribed to produce the mRNA for the polypeptide or a fragment thereof, and optionally translated to produce the polypeptide or a fragment thereof. The antisense strand is the complement of such a nucleic acid, and the encoding sequence can be deduced therefrom. Further, as used herein an amino acid sequence coding sequence refers to a nucleotide sequence encoding the amino acid sequence.

[0062] The term “a regulatory sequence”, “an expression control element” or “promoter” as used herein, intends a polynucleotide that is operatively linked to a target polynucleotide to be transcribed or replicated, and facilitates the expression or replication of the target polynucleotide. A promoter is an example of an expression control element or a regulatory sequence. Promoters can be located 5’ or upstream of a gene or other polynucleotide, that provides a control point for regulated gene transcription. Polymerase II and III are examples of promoters. In some embodiments, a regulatory sequence is bidirectional, i.e., acting as a regulatory sequence for the coding sequences on both sides of the regulatory sequence. Such bidirectional regulatory sequence may comprise, or consists essentially of, or consists of a bidirectional promoter (see for example Trinklein ND, et al. (2004) An abundance of bidirectional promoters in the human genome. Genome Res. Jan;14(l):62-6).

[0063] The term “protein,” “peptide” and “polypeptide” are used interchangeably and in their broadest sense to refer to a compound of two or more subunit amino acids, amino acid analogs or peptidomimetics. The subunits (which are also referred to as residues) may be linked by peptide bonds. In another embodiment, the subunit may be linked by other bonds, e.g., ester, ether, etc. A protein or peptide must contain at least two amino acids and no-11-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 limitation is placed on the maximum number of amino acids which may comprise a protein's or peptide's sequence. As used herein the term “amino acid” refers to either natural and / or unnatural or synthetic amino acids, including glycine and both the D and L optical isomers, amino acid analogs and peptidomimetics.10064] The amino acid single-letter and three-letter codes are found below:Full Name of Amino-Acid Single-Letter Code Three-Letters CodeGlycineGlyAlanineAlaLeucineLeuMethionineMetPhenylalaninePheTryptophanTrpLysineLysGlutamineGinGlutamic AcidGluSerineSerProlineProValineVaiIsoleucineHeCysteineCysTyrosineTyr4927-7786-8905.2Atty. Dkt. No.: 121384-0285Histidine H HisArginine R ArgAsparagine N AsnAspartic Acid D AspThreonine T Thr

[0065] As used herein, the term “antibody” collectively refers to immunoglobulins or immunoglobulin-like molecules including by way of example and without limitation, IgA, IgD, IgE, IgG and IgM, combinations thereof, and similar molecules produced during an immune response in any vertebrate, for example, in mammals such as humans, goats, rabbits and mice, as well as non-mammalian species, such as shark immunoglobulins. Unless specifically noted otherwise, the term “antibody” includes intact immunoglobulins and “antibody fragments” or “antigen binding fragments” that specifically bind to a molecule of interest (or a group of highly similar molecules of interest) to the substantial exclusion of binding to other molecules (for example, antibodies and antibody fragments that have a binding constant for the molecule of interest that is at least 103M'1greater, at least 104M'1greater or at least 105M'1greater than a binding constant for other molecules in a biological sample). The term “antibody” also includes genetically engineered forms such as chimeric antibodies (for example, murine or humanized non-primate antibodies), heteroconjugate antibodies (such as, bispecific antibodies). See also, Pierce Catalog and Handbook, 1994- 1995 (Pierce Chemical Co., Rockford, Ill.); Owen et al., Kuby Immunology, 7th Ed., W.H. Freeman & Co., 2013; Murphy, Janeway’s Immunobiology, 8th Ed., Garland Science, 2014; Male et al., Immunology (Roitt), 8th Ed., Saunders, 2012; Parham, The Immune System, 4th Ed., Garland Science, 2014.

[0066] As used herein, the term “T cell,” refers to a type of lymphocyte that matures in the thymus. T cells play an important role in cell-mediated immunity and are distinguished from other lymphocytes, such as B cells, by the presence of a T-cell receptor on the cell surface. T- cells may either be isolated or obtained from a commercially available source. “T cell” includes all types of immune cells expressing CD3 including T-helper cells (CD4+ cells),-13-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 cytotoxic T-cells (CD8+ cells), natural killer T-cells, T-regulatory cells (Treg) and gammadelta T cells. Additional types of T cells include an invariant natural killer T (iNKT) cell, a mucosal associated invariant T (MAIT) cell, a macrophage, a monocyte, a natural killer (NK) cell, a tumor infiltrating lymphocyte (TIL), a cytotoxic T cell, a T helper cell, a memory T cell, a central memory T (TCM) cell, a stem memory T (TSCM) cell, a stem-cell-like memory T cell (or stem-like memory T cells), an effector memory T (TEM) cell, a TEMRA (CD45RA+) cell, an effector T cell, a Thl cell, a Th2 cell, a Th9 cell, a Th 17 cell, a Th22 cell, a Tfh (follicular helper) cell, a natural killer T (NKT) cell, a transitional memory T (TTM) cell, a terminal effector T (TTE) cell, or a naive T (TN) cell.

[0067] As used herein, the term “sample” refers to clinical samples obtained from a subject. In certain embodiments, a sample is obtained from a biological source (i.e., a “biological sample”), such as tissue, bodily fluid, or microorganisms collected from a subject. Sample sources include, but are not limited to, mucus, sputum, bronchial alveolar lavage (BAL), bronchial wash (BW), whole blood, bodily fluids, cerebrospinal fluid (CSF), urine, plasma, serum, or tissue.

[0068] As used herein, the term “stimulation” refers to a primary response induced by binding of a stimulatory molecule (e.g., a TCR / CD3 complex) with its cognate ligand thereby mediating a signal transduction event, such as, but not limited to, signal transduction via the TCR / CD3 complex. Stimulation can mediate altered expression of certain molecules, such as downregulation of TGFP, and / or reorganization of cytoskeletal structures, and the like.

[0069] Transforming growth factor beta (TGF-P) is a cytokine. It can act as an inducer of CXCL13 (Kobayashi et al. (2016) European Journal of Immunology 46(2): 360-71.

[0070] A “stimulatory molecule,” as the term is used herein, means a molecule on a T cell that specifically binds with a cognate stimulatory ligand present on an antigen presenting cell.

[0071] The term “therapeutically effective amount” refers to the amount of the subject compound that will elicit the biological or medical response of a tissue, system, or subject that is being sought by the researcher, veterinarian, medical doctor or other clinician. The term “therapeutically effective amount” includes that amount of a compound that, when administered, is sufficient to prevent development of, or alleviate to some extent, one or more -14-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 of the signs or symptoms of the disorder or disease being treated. The therapeutically effective amount will vary depending on the compound, the disease and its severity and the age, weight, etc., of the subject to be treated. As used in the methods provided herein, the terms “therapeutically effective amount” and “effective amount” are used interchangeably.10072] “Treating” or “treatment” as used herein covers the treatment of a disease or disorder described herein, in a subject, such as a human, and includes: (i) inhibiting a disease or disorder, i.e., arresting its development; (ii) relieving a disease or disorder, i.e., causing regression of the disorder; (iii) slowing progression of the disorder; and / or (iv) inhibiting, relieving, or slowing progression of one or more symptoms of the disease or disorder. Therapeutic effects of treatment include, without limitation, inhibiting recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, preventing metastases, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis.

[0073] Treatment of cancer or an infection, immune disorder, or autoimmune response, disorder or disease can be at any time during the cancer or an infection, immune disorder, or autoimmune response, disorder or disease. Certain embodiments of the present disclosure can be administered as a combination (e.g., with a second active), or separately concurrently or in sequence (sequentially) in accordance with the methods described herein as a single or multiple dose e.g., one or more times hourly, daily, weekly, monthly or annually or between about 1 to 10 weeks, or for as long as appropriate, for example, to achieve a reduction in the onset, progression, severity, frequency, duration of one or more symptoms or complications associated with or caused by cancer or an infection, immune disorder, or autoimmune response, disorder or disease, or an adverse symptom, condition or complication associated with or caused by cancer or an infection, immune disorder, or autoimmune response, disorder or disease. Thus, a method can be practiced one or more times (e.g., 1-10, 1-5 or 1-3 times) an hour, day, week, month, or year. The skilled artisan will know when it is appropriate to delay or discontinue administration. A non-limiting dosage schedule is 1-7 times per week, for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 or more weeks, and any numerical value or range or value within such ranges.-15-4927-7786-8905.2Atty. Dkt. No.: 121384-0285

[0074] The term “contacting” means direct or indirect binding or interaction between two or more. A particular example of direct interaction is binding. A particular example of an indirect interaction is where one entity acts upon an intermediary molecule, which in turn acts upon the second referenced entity. Contacting as used herein includes in solution, in solid phase, in vitro, ex vivo, in a cell and in vivo. Contacting in vivo can be referred to as administering, or administration.

[0075] The term “antigen spread” (also referred to as “determinant spread” or “epitope spread”) refers to the induction and amplification of an immune response from a dominant antigen to antigens distinct from the original target (secondary antigens). Secondary antigens may be a different epitope of the first antigen, or a different antigen all together. See e.g. El- Sayes et al. (2021) Cancers (Basel). Feb; 13(4): 806, doi: 10.3390 / cancersl3040806 and Ma et al. (2023) Cell 186, 3148-3165, doi.org / 10.1016 / j.cell.2023.06.002.

[0076] CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is an acronym for DNA loci that contain multiple, short, direct repetitions of base sequences. The prokaryotic CRISPR / Cas system has been adapted for use as gene editing (silencing, enhancing or changing specific genes) for use in eukaryotes (see, for example, Cong, Science, 15:339(6121):819-823 (2013) and Jinek, et al., Science, 337(6096): 816-21 (2012)). By transfecting a cell with elements including a Cas gene and specifically designed CRISPRs, nucleic acid sequences can be cut and modified at any desired location. Methods of preparing compositions for use in genome editing using the CRISPR / Cas systems are described in detail in US Pub. No. 2016 / 0340661, US Pub. No. 20160340662, US Pub. No. 2016 / 0354487, US Pub. No. 2016 / 0355796, US Pub. No. 20160355797, and WO 2014 / 018423, which are specifically incorporated by reference herein in their entireties.

[0077] Thus, as used herein, “CRISPR system” refers collectively to transcripts and other elements involved in the expression of or directing the activity of CRISPR-associated (“Cas”) genes, including sequences encoding a Cas gene, a tracr (trans-activating CRISPR) sequence (e.g., tracrRNA or an active partial tracrRNA), a tracr-mate sequence (encompassing a “direct repeat” and a tracrRNA-processed partial direct repeat in the context of an endogenous CRISPR system), a guide sequence (also referred to as a “spacer”, “guide RNA” or “gRNA” in the context of an endogenous CRISPR system), or other sequences and transcripts from a-16-4927-7786-8905.2Atty. Dkt. No.: 121384-0285CRISPR locus. One or more tracr mate sequences operably linked to a guide sequence (e.g., direct repeat-spacer-direct repeat) can also be referred to as “pre-crRNA” (pre-CRISPR RNA) before processing or crRNA after processing by a nuclease.

[0078] In some embodiments, one or more vectors driving expression of one or more elements of a CRISPR system are introduced into a target cell such that expression of the elements of the CRISPR system direct formation of a CRISPR complex at one or more target sites. While the specifics can be varied in different engineered CRISPR systems, the overall methodology is similar. A practitioner interested in using CRISPR technology to target a DNA sequence can insert a short DNA fragment containing the target sequence into a guide RNA expression plasmid. The sgRNA expression plasmid contains the target sequence (about 20 nucleotides), a form of the tracrRNA sequence (the scaffold) as well as a suitable promoter and necessary elements for proper processing in eukaryotic cells. Such vectors are commercially available (see, for example, Addgene). Many of the systems rely on custom, complementary oligos that are annealed to form a double stranded DNA and then cloned into the sgRNA expression plasmid. Co-expression of the sgRNA and the appropriate Cas enzyme from the same or separate plasmids in transfected cells results in a single or double strand break (depending of the activity of the Cas enzyme) at the desired target site.Compositions, Subject Population and Methods of Administration

[0079] As used herein “patient” and “subject” are used interchangeably.

[0080] In the methods described herein, the term “subject” refers includes but is not limited to a subject at risk of an immune disorder, or autoimmune response, disorder or disease, as well as a subject that has already developed an immune disorder, or autoimmune response, disorder or disease. Such subjects, include mammalian animals (mammals), such as a nonhuman primate (apes, gibbons, gorillas, chimpanzees, orangutans, macaques), a domestic animal (dogs and cats), a farm animal (poultry such as chickens and ducks, horses, cows, goats, sheep, pigs), experimental animal (mouse, rat, rabbit, guinea pig) and humans. Subjects include animal disease models, for example, mouse and other animal models of immune disorders, or autoimmune response, disorder or disease known in the art.-17-4927-7786-8905.2Atty. Dkt. No.: 121384-0285

[0081] In some embodiments in the methods described herein, the subject is an adult human. In other embodiments the subject is a juvenile human.

[0082] In the methods described herein, administering a T-cell comprising a mutation, and / or composition can be accomplished by any method known in the art suitable for the particular type of agonist and formulation selected. Suitable routes of administration include without limitation oral, intratumoral, parenteral (including intramuscular, subcutaneous, intradermal, intravascular, intravenous, intraarterial, intraarticular intramedullary and intrathecal), intraperitoneal, and topical (including dermal / epicutaneous, transdermal, mucosal, transrnucosal, intranasal (e.g., by nasal spray or drop), intraocular (e.g., by eye drop), pulmonary (e g., by inhalation), buccal, sublingual, rectal and vaginal ).100831 In some aspects, in the methods described herein, the administering to a subject in need can be done intravenously or subcutaneously. In other aspects, in the methods described herein, the administering to a subject in need can be topical.

[0084] In some aspects of the methods described herein, an additional therapeutic agent is administered to the subject in need. In one embodiment, the additional therapeutic agent is a chemotherapeutic agent.

[0085] Doses in the methods described herein can be based upon current existing protocols, empirically determined, using animal disease models or optionally in human clinical trials. Initial study doses can be based upon animal studies, e.g. a mouse, and the amount treatment or agent disclosed herein administered in an amount that is determined to be effective. Exemplary non-limiting amounts (doses) are in a range of about 0.1 mg / kg to about 100 mg / kg, and any numerical value or range or value within such ranges. Greater or lesser amounts (doses) can be administered, for example, 0.01-500 mg / kg, and any numerical value or range or value within such ranges. The dose can be adjusted according to the mass of a subject, and will generally be in a range from about 1-10 ug / kg, 10-25 ug / kg, 25-50 ug / kg, 50-100 ug / kg, 100-500 ug / kg, 500-1,000 ug / kg, 1-5 mg / kg, 5-10 mg / kg, 10-20 mg / kg, 20-50 mg / kg, 50-100 mg / kg, 100-250 mg / kg, 250-500 mg / kg, or more, two, three, four, or more times per hour, day, week, month or annually. A typical range will be from about 0.3 mg / kg-18-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 to about 50 mg / kg, 0-25 mg / kg, or 1.0-10 mg / kg, or any numerical value or range or value within such ranges.(0086] The maximum tolerable dose of the methods described herein can be readily established, and the effective amount providing a detectable therapeutic benefit to a patient may also be determined, as can the temporal requirements for administering each agent to provide a detectable therapeutic benefit to the patient. Accordingly, while certain dose and administration regimens are exemplified herein, these examples in no way limit the dose and administration regimen that may be provided to a patient in practicing the present disclosure.

[0087] Doses can vary and depend upon whether the treatment is prophylactic or therapeutic, whether a subject has previously had cancer or an infection, immune disorder, or autoimmune response, disorder or disease, the onset, progression, severity, frequency, duration probability of or susceptibility of the symptom, condition, pathology or complication, the treatment protocol and compositions, the clinical endpoint desired, the occurrence of previous or simultaneous treatments, the general health, age, gender, race or immunological competency of the subject and other factors that will be appreciated by the skilled artisan. The skilled artisan will appreciate the factors that may influence the dosage and timing required to provide an amount sufficient for providing a therapeutic or prophylactic benefit.

[0088] In the methods described herein, the route, dose, number and frequency of administrations, treatments, and timing / intervals between treatment and disease development can be modified. In certain embodiments, a desirable treatment of the present disclosure will elicit robust, long-lasting immunity against cancer or an infection, immune disorder, or autoimmune response, disorder or disease. Thus, in certain embodiments, disclosure methods, uses and compositions provide long-lasting immunity to cancer or an infection, immune disorder, or autoimmune response, disorder or disease.

[0089] As used herein the term “pharmaceutically acceptable” and “physiologically acceptable” mean a biologically acceptable formulation, gaseous, liquid or solid, or mixture thereof, which is suitable for one or more routes of administration, in vivo delivery or contact. Such formulations include solvents (aqueous or non-aqueous), solutions (aqueous or non-aqueous), emulsions (e.g., oil-in-water or water-in-oil), suspensions, syrups, elixirs,-19-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 dispersion and suspension media, coatings, isotonic and absorption promoting or delaying agents, compatible with pharmaceutical administration or in vivo contact or delivery. Aqueous and non-aqueous solvents, solutions and suspensions may include suspending agents and thickening agents. Such pharmaceutically acceptable carriers include tablets (coated or uncoated), capsules (hard or soft), microbeads, powder, granules and crystals. Supplementary active compounds (e.g., preservatives, antibacterial, antiviral and antifungal agents) can also be incorporated into the compositions.

[0090] Compositions (i.e. pharmaceutical compositions) described herein can be formulated to be compatible with a particular route of administration. Thus, pharmaceutical compositions include carriers, diluents, or excipients suitable for administration by various routes.Exemplary routes of administration for contact or in vivo delivery which a composition can optionally be formulated include inhalation, respiration, intranasal, intubation, intrapulmonary instillation, oral, buccal, intrapulmonary, intradermal, topical, dermal, parenteral, sublingual, subcutaneous, intravascular, intrathecal, intraarticular, intracavity, transdermal, iontophoretic, intraocular, opthalmic, optical, intravenous (i.v.), intramuscular, intraglandular, intraorgan, or intralymphatic.

[0091] Formulations suitable for parenteral administration comprise aqueous and nonaqueous solutions, suspensions or emulsions of the active compound, which preparations are typically sterile and can be isotonic with the blood of the intended recipient. Non-limiting illustrative examples include water, saline, dextrose, fructose, ethanol, animal, vegetable or synthetic oils.Modes for Carrying out the Disclosure

[0092] Polynucleotide, Vectors, Cells, and Compositions thereof

[0093] According to one embodiment, described herein is a vector comprising a nucleic acid sequence encoding a polypeptide comprising a T cell lymphoma protein mutant or functional fragment thereof. In some aspects, the polypeptide comprises at least one selected from a FAS, FYN-TRAF3IP2, VAV1-STAP2, IL2RG, CTNNB1, CAPRIN-JAK2, mCTLA4- mCD28, IKZF2-ERBB4, PABPC1-TYK2, IL7R, mCD3E, TRAF3, IDH1, JAK3, RPL10, TLDC1, STAT3, DNMT3A, NFKB2, RASGRP1, AKT1, MAPK1, KHDRBS1-LCK, or-20-4927-7786-8905.2Atty. Dkt. No.: 121384-0285VAV-MY01F mutant protein or functional fragment thereof, wherein the protein or functional fragment thereof is a variant of the wild-type protein.(0094] In one aspect, the nucleic acid comprises a sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to at least one of SEQ ID NOs: 1-31.(0095] In some aspects, the variant is a point mutation, a gene fusion, a substitution, a gain- of-function mutation, a stop-gain mutation, an insertion mutation, a deletion mutation, a duplication mutation or a translocation.|0096| Also described herein is a vector comprising a nucleic acid sequence encoding a polypeptide comprising a T cell lymphoma wild-type protein or functional fragment thereof. In some aspects, the polypeptide comprises at least selected from a AKT1, IL2RG, or TBL1IR1 wild-type protein.(0097] In some aspects, the vector is a plasmid, a herpes simplex virus, a retrovirus, an adenovirus, a murine stem cell virus (MSCV) or an adeno-associated virus. In one aspect, the retrovirus is a lentivirus.100981 According to another embodiment, described herein is an engineered cell comprising a nucleic acid sequence encoding a polypeptide, the polypeptide comprising a T cell lymphoma protein mutant or functional fragment thereof. In some aspects, the polypeptide comprises at least one selected from a FAS, FYN-TRAF3IP2, VAV1-STAP2, IL2RG, CTNNB1, CAPRIN-JAK2, mCTLA4-mCD28, IKZF2-ERBB4, PABPC1-TYK2, IL7R, mCD3E, TRAF3, IDH1, JAK3, RPL10, TLDC1, STAT3, DNMT3A, NFKB2, RASGRP1, AKT1, MAPK1, KHDRBS1-LCK, or VAV-MYO1F mutant protein or functional fragment thereof, wherein the protein or functional fragment thereof is a variant of the wild-type protein. In some aspects, the nucleic acid comprises a sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to at least one of SEQ ID NOs: 1-31.

[0099] In some aspects, the variant is a point mutation, a gene fusion, a substitution, a gain- of-function mutation, a stop-gain mutation, an insertion mutation, a deletion mutation, a duplication mutation or a translocation.-21-4927-7786-8905.2Atty. Dkt. No.: 121384-0285

[0100] Also described herein is an engineered cell comprising a nucleic acid sequence encoding a polypeptide comprising a T cell lymphoma wild-type protein or functional fragment thereof. In some aspects, the polypeptide comprises at least selected from a AKT1, IL2RG, TBL1IR1, or IDH1 wild-type protein.10.101] According to another embodiment, described herein is an engineered cell comprising a polypeptide, the polypeptide comprising a T cell lymphoma protein mutant or functional fragment thereof. In some aspects, the polypeptide comprises at least one selected from a FAS, FYN-TRAF3IP2, VAV1-STAP2, IL2RG, CTNNB1, CAPRIN-JAK2, mCTLA4- mCD28, IKZF2-ERBB4, PABPC1-TYK2, IL7R, mCD3E, TRAF3, IDH1, JAK3, RPL10, TLDC1, STAT3, DNMT3A, NFKB2, RASGRP1, AKT1, MAPK1, KHDRBS1-LCK, or VAV-MYO1F mutant protein or functional fragment thereof, wherein the protein or functional fragment thereof is a variant of the wild-type protein.

[0102] In some aspects, the variant is a point mutation, a gene fusion, a substitution, a gain- of-function mutation, a stop-gain mutation, an insertion mutation, a deletion mutation, a duplication mutation or a translocation.

[0103] Also described herein is an engineered cell comprising a polypeptide comprising a T cell lymphoma wild-type protein or functional fragment thereof. In some aspects, the polypeptide comprises at least selected from a AKT1, IL2RG, TBL1IR1, or IDH1 wild-type protein.

[0104] According to one embodiment, the engineered cell comprises the vectors described herein.

[0105] In some aspects, the engineered cell is a T cell. The T cell can be selected from a CAR T cell, CD3+ cell, CD8+ cell, CD4+ cell, regulatory T cell, a gamma delta T cell (y5T), an invariant natural killer T (iNKT) cell, a mucosal associated invariant T (MAIT) cell, a macrophage, a monocyte, a natural killer (NK) cell, a tumor infiltrating lymphocyte (TIL), a cytotoxic T cell, a T helper cell, a memory T cell, a central memory T (TCM) cell, a stem memory T (TSCM) cell, a stem-cell-like memory T cell (or stem-like memory T cells), an effector memory T (TEM) cell, a TEMRA (CD45RA+) cell, an effector T cell, a Thl cell, a Th2 cell, a Th9 cell, a Th 17 cell, a Th22 cell, a Tfh (follicular helper) cell, a natural killer T-22-4927-7786-8905.2Atty. Dkt. No.: 121384-0285(NKT) cell, a transitional memory T (TTM) cell, a terminal effector T (TTE) cell, or a naive T (TN) cell.

[0106] In one aspect, the engineered cell is a CD8 T cell, a Jurkat T cell, or a CAR T cell.

[0107] In some aspects the T cell further comprises a receptor with specificity for a target antigen. The receptor may be a chimeric antigen receptor (CAR) with specificity for a target antigen or a T cell receptor (TCR) having specificity for a target antigen. In other aspects the target antigen is selected from CD 19, B7H3 (CD276), BCMA (CD269), ALPPL2, Claudin 18.2, CD123, CD171, CD179a, CD20, CD213A2, CD22, CD24, CD246, CD272, CD30, CD33, CD38, CD44v6, CD46, CD71, CD97, CEA, Claudin 6(CLDN6), CLECL1, CS-1, DLL-3, EGFR, EGFRvIII, ELF2M, EpCAM, EphA2, Ephrin B2, FAP, FLT3, GCC, GD2, GD3, GM3, GPRC5D, HER2 (ERBB2 / neu), IGLL1, IL-l lRa, KIT (CD117), KLK2, LY6G6D, MUC1, NCAM, p53R175H, PAP, PDGFR-P, PRAME, PRSS21, PSCA, PSMA, R0R1, SIRPa, SSEA-4, TAG72, TEM1 / CD248, TEM7R, TSHR, VEGFR2, ALPI, citrullinated vimentin, cMet, and / or Axl. In yet other aspects the target antigen is selected from cell surface receptors, adhesion proteins, integrins, mucins, lectins, tumor-associated antigens, and tumor-specific antigens.101081 In some aspects, the engineered cell has increased or decreased signaling through the API, NF AT, KFKB, and / or PD1 pathways as compared to a cell of the same type without the nucleic acid or polypeptide. In one aspect, the engineered cell has increased signaling through the API, NF AT, KFKB, and / or PD1 pathways as compared to cell of the same cell type without the nucleic acid or polypeptide. See FIG. 8C.] 0109] In some aspects, the engineered cell has increased or decreased cytokine production as compared to a cell of the same type without the nucleic acid or polypeptide. In one aspect, the engineered cell has increased cytokine production as compared to a cell of the same type without the nucleic acid or polypeptide. In some aspects, the cytokine is selected from IL-2, IL-4, 11-5, TNF alpha, IFN- gamma and / or IL-13. See FIGS. 8B.

[0110] Also provided herein is a composition comprising the engineered cell. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier. In-23-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 some embodiments, the composition further comprises additional agents, including therapeutic drug agents.10111] Variants in the polypeptides, vectors, and cells

[0112] According to some aspects, the T cell lymphoma wild-type protein or variant provided herein is selected from a wild-type protein or variant in Table 1 or Table 5. In one aspect, the selected variant has higher expression in the tumor microenvironment and / or tumor draining lymph nodes than the negative control. See e.g., FIGS. 3-5. The negative control can be a vector or engineered cell that does not comprise the wild-type protein or variant, or nucleotide encoding the wild-type protein or variant.{0113] According to some aspects, the wild-type protein or protein variant provided herein is selected from: a) FAS substitution at amino acid 265; b) FYN-TRAF3IP2 fusion; c) VAV1-STAP2 fusion; d) IL2RG substitution at amino acid 315; e) CTNNB1 substitution at amino acid 45; f) CAPRIN-JAK2 fusion; g) mCTLA4-mCD28 fusion; h) IKZF2-ERBB4 fusion; i) PABPC1-TYK2 fusion; j) IL7R mutation T244I245CPT; k) mCD3E substitution at amino acid 34; l) TRAF3 substitution at amino acid 359;-24-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 m) IDH1 substitution at amino acid 132; n) JAK3 substitution at amino acid 572, 583, or 589; o) RPL10 substitution at amino acid 98 p) TLDC1 substitution at amino acid 587; q) STAT3 substitution at amino acid 618; r) DNMT3 A substitution at amino acid 882; s) IL7R substitution at amino acid 78; t) NFKB2 substitution at amino acid 882; q) RASGRP1 substitution at amino acid 261; r) AKT1 substitution at amino acid 17; s) MAPK1 substitution at amino acid 321; t) KHDRBS1-LCK fusion; u) VAV1-MY01F fusion v) AKT1 wild-type w) IL2RG wild-type; and / or x) TBL1XR1 WT.

[0114] According to some aspects, the protein is encoded by a nucleotide selected from the the sequences of SEQ ID NOs: 1-31. According to some aspects, the nucleic acid comprises a sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to at least one of SEQ ID NOs: 1-31.

[0115] According to some aspects, the protein is a variant of the wild type amino acid sequence.-25-4927-7786-8905.2Atty. Dkt. No.: 121384-0285

[0116] According to one aspect, the variant is naturally occurring. According to another aspect, the variant is non-naturally occurring.[0117| FAS

[0118] As used herein, FAS refers to the tumor necrosis factor receptor superfamily member 6 protein and is encoded by the FAS gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_009089.2 or NP_000034.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wildtype FAS can have a sequence according to accession number according to ENST00000652046.1, which is 335 amino acids in length. ENST00000652046.1 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1 and encodes a FAS polypeptide with a D265E substitution. In some embodiments, the polypeptide is FAS polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000652046.1 includes a substitution at amino acid 265, wherein amino acid 265 is determined using the full length sequence of ENST00000652046.1 . In one embodiment the substitution is a D265E substitution.

[0119] FYN10120] As used herein, FYN refers to tyrosine-protein kinase Fyn and is encoded by the FYN gene or a fragment thereof. A non-limiting exemplary sequence of this protein may be found under NCBI NP_001357458.1, which is incorporated by reference herein in its entirety. In some embodiments, the wildtype FYN can have a sequence according to accession number according to ENST00000354650.7, which is 537 amino acids in length.

[0121] TRAF3IP2-26-4927-7786-8905.2Atty. Dkt. No.: 121384-0285

[0122] As used herein, TRAF3IP2 refers to the E3 ubiquitin ligase TRAF3IP2 and is encoded by the TRAF3IP2 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 032030.2 or NP_001157753.1, each of which is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2 and encodes a FYN-TRAF3IP2 fusion polypeptide. In one embodiment, the polypeptide is a FYN-TRAF3IP2 fusion polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 32.

[0123] VAV1

[0124] As used herein, VAV1 refers to the proto-oncogene vav and is encoded by the VAV1 gene or a fragment thereof. A non-limiting exemplary sequence of this protein may be found under NCBI NP_001245135.1, which is incorporated by reference herein in its entirety. In some embodiments, the wildtype VAV1 can have a sequence according to accession number according to ENST00000602142.6, which is 845 amino acids in length.

[0125] MYO IF

[0126] As used herein, MYO1F refers to myosin IF and is encoded by the MYO1F gene or a fragment thereof. A non-limiting exemplary sequence of this protein may be found under NP 036467.2, which is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 31 and encodes a VAV1-MYO1F fusion polypeptide. In one embodiment, the polypeptide is a VAV1-MYO1F fusion polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 40.

[0127] STAP2-27-4927-7786-8905.2Atty. Dkt. No.: 121384-0285

[0128] As used herein, STAP2 refers to the signal-transducing adaptor protein 2 and is encoded by the STAP2 gene or a fragment thereof. A non-limiting exemplary sequence of this protein may be found under NCBI NP 001013863.1, which is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3 and encodes a VAV1-STAP2 fusion polypeptide. In one embodiment, the polypeptide is a VAV1-STAP2 fusion polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 33.[0129[ IL2RG

[0130] As used herein, IL2RG refers to the cytokine receptor common subunit gamma, also known as interleukin 2 receptor, gamma, and is encoded by the IL2RG gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_009088.1 or NP_000197.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wildtype IL2RG can have a sequence according to accession number according to ENST00000374202.7, which is 369 amino acids in length. ENST00000374202.7 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 4 and encodes a wildtype IL2RG polypeptide. In some embodiments, the polypeptide is a IL2RG polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000374202.7. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 5 and encodes a IL2RG-28-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 polypeptide with a K315E substitution. In some embodiments, the polypeptide is a IL2RG polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity the amino acid sequence according to ENST00000374202.7 and includes a substitution at amino acid 315, wherein amino acid 315 is determined using the full length sequence of ENST00000374202.7. In one embodiment the substitution is a K315E substitution.

[0131] CTNNB1

[0012] As used herein, CTNNB1 refers to the catenin beta-1 protein and is encoded by the CTNNB1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 013302.2 or NP 001091679.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wildtype CTNBB1 can have a sequence according to accession number according to ENST00000645276.1, which is 784 amino acids in length.ENST00000645276.1 is incorporated by reference herein in its entirety In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 6 and encodes a CTNNB1 polypeptide with a S45F substitution. In some embodiments, the polypeptide is a CTNNB1 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000645276.1 and includes a substitution at amino acid 45, wherein amino acid 45 is determined using the full length sequence of ENST00000645276.1. In one embodiment the substitution is a S45F substitution.10133] CAPRIN10.134] As used herein, CAPRIN refers to GPI-anchored membrane protein 1; caprin-1 and is encoded by the CAPRIN1 gene or a fragment thereof. A non-limiting exemplary sequence of4927-7786-8905.2Atty. Dkt. No.: 121384-0285 this protein may be found under NP 005889.3, which is incorporated by reference herein in its entirety.

[0135] JAK2

[0136] As used herein, JAK2, refers to tyrosine-protein kinase JAK2 and is encoded by the JAK2 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 009904.1 or NP 001309123.1, each of which is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 7 and encodes a CAPRIN-JAK2 fusion polypeptide. In one embodiment, the polypeptide is a CAPRIN-JAK2 fusion polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 34.

[0137] CTLA4

[0138] As used herein, CTLA4 refers to cytotoxic T-lymphocyte protein 4 and is encoded by the CTLA4 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_011502.1 or NP_001032720.1, each of which is incorporated by reference herein in its entirety. mCTLA4 refers to murinized CTLA4.

[0139] CD28

[0140] As used herein, CD28 refers to T-cell-specific surface glycoprotein CD28 and is encoded by the CD28 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 029618.1 or NP_001230006.1, each of which is incorporated by reference herein in its entirety. mCD28 refers to murinized CD28. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%-30-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 sequence identity to SEQ ID NO: 8 and encodes a mCTLA4-mCD28 fusion polypeptide. In one embodiment, the polypeptide is a mCTLA4-mCD28 fusion polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 35.[01411 IKZF2101.421 As used herein, IKZF2 refers to the zinc finger protein Helios and is encoded by the IKZF2 gene or a fragment thereof. A non-limiting exemplary sequence of this protein may be found under NCBI NP 001072994.1, which is incorporated by reference herein in its entirety.

[0143] ERBB4

[0144] As used herein, ERBB4 refers to the receptor tyrosine-protein kinase erbB-4 and is encoded by the ERBB4 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_011805.2 or NP_001036064.1, each of which is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 9 and encodes a IKZF2-ERBB4 fusion polypeptide. In one embodiment, the polypeptide is a IKZF2-ERBB4 fusion polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 36.|0145| PABPC1

[0146] As used herein, PABPC1, refers to polyadenylate-binding protein 1 and is encoded by the PABPClgene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_027520.1 or NP_002559.2, each of which is incorporated by reference herein in its entirety.-31-4927-7786-8905.2Atty. Dkt. No.: 121384-0285[0147| TYK2

[0148] As used herein, TYK2 refers to non-receptor tyrosine-protein kinase TYK2 and is encoded by the TYK2 gene or a fragment thereof. A non-limiting exemplary sequence of this protein or the underlying gene or functions thereof may be found under NCBI NG 007872.1 or NP_001372126.1, which is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 10 and encodes PABPC1-TYK2 fusion polypeptide. In one embodiment, the polypeptide is a PABPC1-TYK2 fusion polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 37.[0149[ IL7R

[0150] As used herein, IL7R, refers to the interleukin-7 receptor subunit alpha protein and is encoded by the IL7R gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 009567.1 or NP 001397663.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wildtype IL7R can have a sequence according to accession number according to ENST00000303115.8, which is 459 amino acids in length.ENST00000303115.8 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 11 and encodes a IL7R polypeptide with a T244I245CPT mutation. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 25 and encodes a IL7R polypeptide with a V78M mutation. In some embodiments, the polypeptide is a IL7R polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%,-32-4927-7786-8905.2Atty. Dkt. No.: 121384-028596%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000303115.8 and includes a C, P, and T insertion between amino acid 244 and 245, wherein amino acid 245 is determined using the full length sequence ofENST00000303115.8. In some embodiments, the polypeptide is a IL7R polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000303115.8 and includes a substitution at amino acid 78, wherein amino acid 78 is determined using the full length sequence of ENST00000303115.8. In one embodiment the substitution is a V78M substitution.[0151| CD3E

[0152] As used herein, CD3E, refers to the T-cell surface glycoprotein CD3 epsilon chain protein and is encoded by the CD3E gene or a fragment thereof. A non-limiting exemplary sequence of this protein or the underlying gene or functions thereof may be found under NCBI NG_007383.1 or NP_000724.1, each of which is incorporated by reference herein in its entirety. mCD3E is murinized CD3E. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 12 and encodes a mCD3E polypeptide with a S34C substitution. In some embodiments, the polypeptide is a mCD3E polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 38 and includes a substitution at amino acid 34. In one embodiment the substitution is a S34C substitution.

[0153] TRAF3

[0154] As used herein, TRAF3, refers to the TNF receptor-associated factor 3 protein and is encoded by the TRAF3 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_027973.1 or NP_001186356.1, each of which is incorporated by reference herein in its-33-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 entirety. In some embodiments, the wildtype IL7R can have a sequence according to accession number according to ENST00000539721.5, which is 486 amino acids in length. ENST00000539721.5 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 13 and encodes a TRAF3 polypeptide with a S359R substitution. In some embodiments, the polypeptide is a TRAF3 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000539721.5 and includes a substitution at amino acid 359, wherein amino acid 359 is determined using the full length sequence of ENST00000539721.5. In one embodiment the substitution is a S359R substitution.|O155] IDH1

[0156] As used herein, IDH1, refers to the isocitrate dehydrogenase [NADP] cytoplasmic protein and is encoded by the IDHlgene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_023319.2 or NP_001269315.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wildtype IDH1 can have a sequence according to accession number according to ENST00000446179.5, which is 415 amino acids in length. ENST00000446179.5 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 17 and encodes a wildtype IDH1 polypeptide. In some embodiments, the polypeptide is a IDH1 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000446179.5.In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%,-34-4927-7786-8905.2Atty. Dkt. No.: 121384-028586%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 14 and encodes a IDH1 polypeptide with a R132C substitution. In some embodiments, the polypeptide is a IDH1 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000446179.5and includes a substitution at amino acid 132, wherein amino acid 132 is determined using the full length sequence ENST00000446179.5. In one embodiment the substitution is a R132C substitution.10157] AKT110158 ] As used herein, AKT1 refers to RAC-alpha serine / threonine-protein kinase and is encoded by the AKT1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 012188.1 or NP 001014431.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wildtype AKT1 can have a sequence according to accession number according to ENST00000349310.7, which is 480 amino acids in length.ENST00000349310.7 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 15 and encodes a wildtype AKT1. In some embodiments, the polypeptide is a AKT1 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid according to ENST00000349310.7. In some embodiments, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 28 and encodes an AKT1 polypeptide with a E17K substitution. In some embodiments, the polypeptide is a AKT1 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%,-35-4927-7786-8905.2Atty. Dkt. No.: 121384-028592%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000349310.7 and includes a substitution at amino acid 17, wherein amino acid 17 is determined using the full length sequence ENST00000349310.7. In one embodiment the substitution is a E17K substitution.|0159] TBL1XR110160] As used herein, TBL1XR1 refers to F-box-like / WD repeat-containing protein TBL1XR1 and is encoded by the TBL1XR1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG_047195.1 or NP_001308122.1, each of which is incorporated by reference herein in its entirety. In some embodiments, the wildtype TBLIXRlcan have a sequence according to accession number according to ENST00000430069.5, which is 514 amino acids in length. ENST00000430069.5 is incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 16 and encodes a wildtype TBL1XR1 polypeptide. In some embodiments, the polypeptide is a TBL1XR1 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000430069.5.| O161] RPL10|0162] As used herein, RPL10 refers to ribosomal protein L10 and is encoded by the RPL10 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NC_000023.11, which is incorporated by reference herein in its entirety. In some embodiments, the wildtype RPL10 have a sequence according to accession number according to ENST00000369817.6, which is 214 amino acids in length. ENST00000369817.6 is incorporated by reference herein in its entirety. In some embodiments, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%,-36-4927-7786-8905.2Atty. Dkt. No.: 121384-028590%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 21 and encodes an RPL10 polypeptide with a R98S substitution. In some embodiments, the polypeptide is a RPL10 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000369817.6 and includes a substitution at amino acid 98, wherein amino acid 98 is determined using the full length sequence ENST00000369817.6. In one embodiment the substitution is a R98S substitution.

[0163] TLDC1

[0014] As used herein, TLDC1 refers to MEAK7 (MTOR associated protein, eak-7 homolog) and is encoded by the TLDC1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NP 065998.3, which is incorporated by reference herein in its entirety. In some embodiments, the wildtype TLDC1 has a sequence according to accession number according to ENST00000343629.10, which is 456 amino acids in length. ENST00000343629.10 is incorporated by reference herein in its entirety. In some embodiments, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 22 and encodes an TLDC1 polypeptide with a S87F substitution. In some embodiments, the polypeptide is a TLDC1 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000343629.10 and includes a substitution at amino acid 87, wherein amino acid 87 is determined using the full length sequence ENST00000343629.10. In one embodiment the substitution is a S87F substitution.

[0165] STAT3

[0166] As used herein, STAT3 refers to signal transducer and activator of transcription 3 and is encoded by the STAT3 gene or a fragment thereof. Non-limiting exemplary sequences of-37-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 this protein or the underlying gene or functions thereof may be found under NC 000017.11 Reference GRCh38.pl4 Primary Assembly or XP_047292542.1, which are incorporated by reference herein in their entirety. In some embodiments, the wildtype STAT3 has a sequence according to accession number according to ENST00000264657, which is 770 amino acids in length. ENST00000264657 is incorporated by reference herein in its entirety. In some embodiments, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 23 and encodes an STAT3 polypeptide with a G618R substitution. In some embodiments, the polypeptide is a STAT3 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000264657 and includes a substitution at amino acid 618, wherein amino acid 618 is determined using the full length sequence ENST00000264657. In one embodiment the substitution is a G618R substitution.

[0167] DNMT3A

[0018] As used herein, DNMT3A refers to DNA methyltransferase 3 alpha and is encoded by the DNMT3 A gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NC 060926.1 Alternate T2T- CHM13v2.0 or XP 054196876.1, which are incorporated by reference herein in their entirety. In some embodiments, the wildtype DNMT3 A has a sequence according to accession number according to ENST00000321117.9, which is 913 amino acids in length. ENST00000321117.9 is incorporated by reference herein in its entirety. In some embodiments, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 24 and encodes an DNMT3 A polypeptide with a R882H substitution. In some embodiments, the polypeptide is a DNMT3 A polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino-38-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 acid sequence according to ENST00000321117.9 and includes a substitution at amino acid 882, wherein amino acid 882 is determined using the full length sequenceENST00000321117.9. In one embodiment the substitution is a R882H substitution.

[0169] NFKB2

[0170] As used herein, NFKB2 refers to nuclear factor kappa B subunit 2 and is encoded by the NFKB2 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NG 033874.2 orNP 001070962.1, which are incorporated by reference herein in their entirety. In some embodiments, the wildtype NFKB2 has a sequence according to accession number according to ENST00000369966.7, which is 900 amino acids in length. ENST00000369966.7 is incorporated by reference herein in its entirety. In some embodiments, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 26 and encodes an NFKB2 polypeptide with a P882Q substitution. In some embodiments, the polypeptide is a NFKB2 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000369966.7 and includes a substitution at amino acid 882, wherein amino acid 882 is determined using the full length sequence ENST00000369966.7. In one embodiment the substitution is a P882Q substitution.

[0171] RASGRP1[01721 As used herein, RASGRP1 refers to RAS guanyl releasing protein 1 and is encoded by the RASGRP1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NG 023268.2 or NP_001122074.1, which are incorporated by reference herein in their entirety. In some embodiments, the wildtype RASGRP1 has a sequence according to accession number according to ENST00000310803.10, which is 797 amino acids in length.ENST00000310803.10 is incorporated by reference herein in its entirety. In some-39-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 embodiments, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 27 and encodes an RASGRP1 polypeptide with a M261I substitution. In some embodiments, the polypeptide is a RASGRP1 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000310803.10 and includes a substitution at amino acid 261, wherein amino acid 261 is determined using the full length sequenceENST00000310803.10. In one embodiment the substitution is a M261I substitution.

[0173] MAPK1

[0174] As used herein, MAPK1 refers to mitogen-activated protein kinase 1 and is encoded by the MAPK1 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NG 023054.2 or NP 002736.3, which are incorporated by reference herein in their entirety. In some embodiments, the wildtype MAPK1 has a sequence according to accession number according to ENST00000215832.10, which is 360 amino acids in length. ENST00000215832.10 is incorporated by reference herein in its entirety. In some embodiments, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 29 and encodes an MAPK1 polypeptide with a D321G substitution. In some embodiments, the polypeptide is a MAPK1 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000215832.10 and includes a substitution at amino acid 321, wherein amino acid 321 is determined using the full length sequence ENST00000215832.10. In one embodiment the substitution is a D321G substitution.

[0175] JAK3-40-4927-7786-8905.2Atty. Dkt. No.: 121384-0285

[0176] As used herein, JAK3 refers to Janus kinas 3 and is encoded by the JAK3 gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NG_007273.1 or NP_000206.2, which are incorporated by reference herein in their entirety. In some embodiments, the wildtype JAK3 has a sequence according to accession number according to ENST00000527670.5, which is 1124 amino acids in length. ENST00000527670.5 is incorporated by reference herein in its entirety. In some embodiments, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 18 and encodes an JAK3 polypeptide with a A572T substitution. In some embodiments, the polypeptide is a JAK3 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000527670.5 and includes a substitution at amino acid 572, wherein amino acid 572 is determined using the full length sequence according to ENST00000527670.5. In one embodiment the substitution is a A572T substitution. In some embodiments, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 19 and encodes an JAK3 polypeptide with a G589D substitution. In some embodiments, the polypeptide is a JAK3 polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000527670.5 and includes a substitution at amino acid 589, wherein amino acid 589 is determined using the full length sequence ENST00000527670.5. In one embodiment the substitution is a G589D substitution. In some embodiments, the nucleic acid sequence is a nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 20 and encodes an JAK3 polypeptide with a H583Y substitution. In some embodiments, the polypeptide is a JAK3 polypeptide including an amino acid sequence having at least a-41-4927-7786-8905.2Atty. Dkt. No.: 121384-028575%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to the amino acid sequence according to ENST00000527670.5 and includes a substitution at amino acid 583, wherein amino acid 583 is determined using the full length sequence ENST00000527670.5. In one embodiment the substitution is a H583Y substitution.

[0177] KHDRBS1

[0178] As used herein, KHDRBS1, refers to KH RNA binding domain containing, signal transduction associated 1 and is encoded by the KHDRBS1 gene or a fragment thereof. Nonlimiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NP 001258807.1, which is incorporated by reference herein in its entirety.

[0179] LCK

[0180] As used herein, LCK refers to LCK proto-oncogene, Src family tyrosine kinase and is encoded by the LCK gene or a fragment thereof. Non-limiting exemplary sequences of this protein or the underlying gene or functions thereof may be found under NCBI NG 023387.1 or NP 001036236.1, each of which are incorporated by reference herein in its entirety. In one embodiment, the nucleic acid sequence is an nucleic acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 30 and encodes a KHDRBS1-LCK fusion polypeptide. In one embodiment, the polypeptide is a KHDRBS1-LCK Fusion polypeptide including an amino acid sequence having at least a 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 39.

[0181] Methods of Generating Vectors

[0182] According to another embodiment, described herein is a method of generating a vector. The method comprises, consists essentially of, or yet further consists of transferring a plasmid to a cell, wherein the plasmid comprises at least one of a) a T cell lymphoma wild--42-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 type protein or functional fragment thereof, or b) a T cell lymphoma protein mutant or functional fragment thereof, wherein the T cell lymphoma protein mutant or functional fragment thereof is a variant of the wild-type protein or functional fragment thereof.

[0183] In one aspect the plasmid comprises a nucleotide encoding a polypeptide comprising at least one selected from a FAS, FYN-TRAF3IP2, VAV1-STAP2, IL2RG, CTNNB1, CAPRIN-JAK2, mCTLA4-mCD28, IKZF2-ERBB4, PABPC1-TYK2, IL7R, mCD3E, TRAF3, IDH1, JAK3, RPL10, TLDC1, STAT3, DNMT3A, NFKB2, RASGRP1, AKT1, MAPK1, KHDRBS1-LCK, or VAV-MYO1F mutant protein or functional fragment thereof. In another aspect the plasmid comprises a nucleotide encoding a polypeptide comprising at least one selected from an AKT1, IL2RG, TBL1XR1, or IDH1 wild-type protein or functional fragment thereof.

[0184] According to some aspects, the protein is encoded by a nucleotide selected from the sequences of SEQ ID NOs: 1-31. According to some aspects, the nucleic acid comprises a sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to at least one of SEQ ID NOs: 1-31.

[0185] In one aspect the vector is a retrovirus, optionally a lentivirus. In some embodiments, the retrovirus is a murine stem cell virus (MSCV).

[0186] Methods of Use

[0187] According to one embodiment, described herein is a method to increase the persistence of T cells in a tumor microenvironment. The method comprises, or consists essentially of, or yet further consists of contacting the tumor with the engineered T cell or composition described herein. In one aspect the tumor microenvironment is a solid tumor microenvironment. In some aspects, the contacting is in vitro or in vivo. See e.g., FIG. 3.

[0188] According to one embodiment, described herein is a method to increase the persistence of T cells in a cancer cell. The method comprises, or consists essentially of, or yet further consists of contacting the cancer cell with the engineered T cell or composition described herein. In one aspect the tumor microenvironment is a solid tumor microenvironment. In some aspects, the contacting is in vitro or in vivo.-43-4927-7786-8905.2Atty. Dkt. No.: 121384-0285[0189| According to another embodiment, described herein is a method to increase the persistence of T cells in a tumor microenvironment or tumor draining lymph nodes of a subject in need thereof. The method comprises, or consists essentially of, or yet further consists of administering to the subject in need the engineered T cell or composition described herein. See e.g., FIGS. 3-7.[01901 According to yet another embodiment, described herein is a method to prevent tumor recurrence in a subject in need thereof. The method comprises, or consists essentially of, or yet further consists of administering to the subject in need the engineered cell or composition described herein after a subject has reduced tumor growth or symptoms. In some aspects, the subject is in partial or complete remission. See e.g., FIGS. 12-1310191 ] In some aspects, the cancer is a solid tumor. The cancer can be selected from small cell lung cancer, colorectal cancer, testicular cancer, ovarian cancer, melanoma, lymphoma, leukemia, multiple myeloma, prostate cancer, breast cancer, non-small cell lung cancer, gastric cancer, esophageal cancer, liver cancer, kidney cancer, head & neck cancer, glioblastoma, neuroblastoma, soft tissue sarcoma, uterine cancer, brain cancer, skin cancer, renal cancer, bladder cancer, pancreatic cancer, thyroid cancer, eye cancer, gastrointestinal cancer, carcinoma, or sarcoma.[01921 According to another embodiment, described herein is a method to inhibit the growth of a cancer and / or increase the survival rate of a subject in need thereof. The method comprises, or consists essentially of, or yet further consists of administering to the subject in need the engineered cell or composition described herein, wherein the cancer comprises an antigen recognized by the T cell. In one aspect, the cancer is a first cancer, and growth of a second cancer is also inhibited after the administration of the engineered cell or composition. The first and second cancer can be the same or different. In some embodiments, first and / or second cancer are a tumor, optionally a solid tumor. In one aspect the second cancer is negative for the T-cell dependent antigen. See e.g., FIGS. 10-13.[ 01 31 In one aspect, administration of the engineered cell or composition can prime the long term immunity of a subject in need against a cancer. See e.g., FIGS. 12-13.-44-4927-7786-8905.2Atty. Dkt. No.: 121384-0285

[0194] In some aspects, administration of the T-cell or composition described herein is administration is parenteral (including intramuscular, subcutaneous, intradermal, intravascular, intravenous, intraarterial, intramedullary and intrathecal), intraperitoneal, or intratumoral .

[0195] In some aspects, the first and / or second cancer is a small cell lung cancer, colorectal cancer, testicular cancer, ovarian cancer, melanoma, lymphoma, leukemia, multiple myeloma, prostate cancer, breast cancer, non-small cell lung cancer, gastric cancer, esophageal cancer, liver cancer, kidney cancer, head & neck cancer, glioblastoma, neuroblastoma, soli tissue sarcoma, uterine cancer, brain cancer, skin cancer, renal cancer, bladder cancer, pancreatic cancer, thyroid cancer, eye cancer, gastrointestinal cancer, carcinoma, or sarcoma.

[0196] In some aspects, the subject in need is a mammal, optionally a human.

[0197] Kils

[0198] As set forth herein, the present disclosure provides methods for administering engineered cells and compositions to a cancer cell, tumor, or subject in need. In one aspect, the present disclosure provides kits for performing these methods as well as instructions for carrying out the methods of the present disclosure.

[0199] In one aspect, the kit comprises, or alternatively consists essentially of, or yet further consists of, any one or more of: a vector as disclosed herein, an engineered cell as disclosed herein, or a composition as disclosed herein, or an optional instruction of use. Such a kit may also comprise, or alternatively consist essentially of, or yet further comprise media and oter reagents appropriate for the methods disclosed herein.(0200] The kits of this disclosure can also comprise, e.g., a buffering agent, a preservative or a protein-stabilizing agent. The kits can further comprise components necessary for detecting the detectable-label, e.g., an enzyme or a substrate. The kits can also contain a control sample or a series of control samples, which can be assayed and compared to the test sample. Each component of a kit can be enclosed within an individual container and all of the various containers can be within a single package, along with instructions for interpreting the results-45-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 of the assays performed using the kit. The kits of the present disclosure may contain a written product on or in the kit container. The written product describes how to use the reagents contained in the kit.

[0201] As amenable, these suggested kit components may be packaged in a manner customary for use by those of skill in the art. For example, these suggested kit components may be provided in solution or as a liquid dispersion or the like.Experimental

[0202] Applicant has found mutations in T cell genes that power T cell therapies. Applicant has found multiple nucleic acid sequences that when expressed by T cells in adoptive T cell therapies increase the persistence in T cells in the solid tumor microenvironment. These genes include STAT5B, FYN-TRAF3IP2, AKT1, VAV1, CTNNB1, CAPRIN-JAK2, and JUNB. The schematic for the in vivo solid tumor is seen in FIG. 9. In in vitro testing, Applicant demonstrated the mutations increase NF-kB and IL-2 in an antigen-dependent manner.

[0203] Applicant demonstrated that the nucleic acid sequences when expressed by T cells in adopt T cell therapies increased proliferation in an antigen-dependent manner. Controls in these assays were vectors expressing mCherry.

[0204] For example, CAPRIN-JAK2 fusion mutants (FIGS. 9-10) enabled durable response. FYN-TRAF3IP2 fusion mutants (FIGS. 11-13) enabled durable response and defense against rechallenge, and enabled antigen spread, inducing clearance of both antigen-specific and antigen-negative tumors.

[0205] CD8+ T cells were isolated from OT-I TCR transgenic mice. These cells were transduced with a murine stem cell virus (MSCV) retrovirus encoding the genes listed in FIG. 14 or FIG. 15 (FC refers to Fold-Change). 1 million cells were transferred into mice bearing B16-F10 cells that express the cognate antigen for OT-I, ovalbumin. 7 days after transfer, the T cells were isolated and subjected to droplet-based single cell RNA-seq utilizing lOx Genomics 5’ RNA-Seq (SKU number) with cell surface antibodies (BioLegend TotalSeq C proteome). The libraries were isolated, sequenced as recommended by the-46-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 manufacturer. The data was processed by CellRanger 8.1.0 with modified GRCm39 as reference. The data analyzed by scanpy 1.10.3. We identified differentially expressed genes between each perturbation and the MSCV vector controls using an adjusted p value cutoff of 0.05. We are listing the cytokines in FIG. 14 and chemokines / chemokine receptors in FIG.15

[0206] At the same time, we cultured CD3+ T cells from healthy donors with a lentivirus encoding each of the mutations listed in FIG. 16 and a lentivirus encoding a chimeric antigen receptor targeting CD 19 (CAR), Kymriah®. After resting the cells in 50U / ml IL2, we cultured the cells with vesicles expressing the cognate antigen (CD 19) for 4 hours (A4) or 24 hours (A24) or with antigen negative control vesicles for 4 hours (N4) or 24 hours (N24). The samples were processed and mRNA were quantified. Differentially expressed genes were identified by DE-Seq2.0. Cytokines are listed in FIG. 16 and chemokines / chemokine receptors are shown in FIG. 17 (FC refers to Fold-Change).

[0207] Materials and Methods

[0208] Genes'. The genes of the wild-type and mutant variants screened represent pathways including the MAPKZERK Pathway, PI3K-AKT Pathway, JAK-STAT / Cytokine Signaling Pathway, Wnt Signaling Pathway, NF-kB Signaling Pathway, Cell Cycle, Apoptosis, Epigenetic / DNA Methylation, mTOR Signaling Pathway, T-Cell Receptor Signaling, Transcription Regulation, RNA Processing, and Metabolism. Applicant selected gene variants that occurred more often than expected by chance.

[0209] Codon Optimization', codon optimization was performed on selected gene variants. See e.g. Fu et al., https: / / www.nature.com / articles / s41598-020-74091-z (2020) for codon optimization, which is incorporated herein in its entirety. Codon optimization plays a role in determining protein expression.

[0210] Tumor models: Applicant generated a syngeneic tumor bearing mice. C57BL / 6 mice obtained from Jackson Labs were inoculated subcutaneously with 0.5M B16-F10 melanoma cells that were transduced with a 51 lb vector expressing both eGFP and ovalbumin proteins.-47-4927-7786-8905.2Atty. Dkt. No.: 121384-0285[0211 | In vivo retroviral screen'. Applicant cloned each of the cDNAs which encompass wild-type cDNAs as well as mutant isoforms into a barcoded murine retroviral vector. Applicant generated pools of these viruses and transduced murine T cells expressing a T cell receptor that recognizes an ovalbumin antigen, OT-I. These cells were transferred to tumor bearing mice on day 7 when the tumors were on average 100 mmA3 in size. After 7 days, the tumors were harvested, the transferred cells were isolated using cell surface markers. They were processed into genomic DNA. The barcodes were PCR amplified and sequenced by next-generation sequencing. The samples were then processed by MAGECK 2.0 to identify statistically significant genes and mutations. Positive log fold change, indicated by LFC, on tables labeled Tables 1 and 4 indicate enrichment in the solid tumor microenvironment.

[0212] Cells from tumor draining lymph nodes in the tumor bearing mice were assessed in a similar way to identify statistically significant genes and mutations.

[0213] In Vitro Validation'. For assessing the impact of the statistically significant mutations on signaling, Applicant cloned these cDNAs into a barcoded lentivirus and transduced Jurkat cells that express fluorescent reporter genes that have promoters and measure the activity of NF AT, NF-kB, and API signaling pathways. These Jurkat cells are also expressing a chimeric antigen receptor that recognizes CD 19. These cells are co-cultured with target cells (such as K562 cells) that express CD 19 (antigen-positive) or not (antigen-negative).

[0214] In Vivo Validation'. To assess effects on persistence and expansion, Applicant measured the numbers of the cells expressing the mutations or controls. To do this Applicant transduced OT-I cells with a retrovirus encoding the mutation of interest or an empty retroviral control. Applicant mixed these cells and transferred them into tumor bearing mice 9 days after tumor cell implantation. 7 days after transfer, the tumors were harvested, dissociated, and T cells were retrieved. Flow cytometry determine the relative ratios of the cells expressing the empty vector or the mutation. This ratio, normalized for differential inputs, reflects the relative enrichment or depletion compared to controls. Statistics were determined by the 2-way ANOVA test.

[0215] Tumor Control: To assess the ability of the potency enhancements to improve tumor control, Applicant transferred the cells expressing a potency enhancement or vector controls-48-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 into tumor bearing mice 9 days after tumor inoculation. Applicant measured tumor growth utilizing digital calipers every 2-3 days and calculated the volume using the formula: length x width x [(length x width)0.5] x K / 6. Applicant assessed the effects of potency enhancements on tumor control using 2-way ANOVA. Applicant also did endpoint analysis utilizing tumor length or width equal to or greater than 15 mm or greater than 50% necrosis of the tumor as clinical endpoints. Survival was measured utilizing Kaplan Meier analysis.

[0216] Peripheral Blood Expansion '. To assess the ability of potency enhancements to engraft and expand in response to antigen, Applicant performed tail vein blood collection every 3-4 days. Percentages of transferred cells were determined using flow cytometry and the congenic marker CD45.1 on transferred cells. Applicant assessed the expansion of potency enhancements in the blood using 2-way ANOVA.

[0217] Transferred Cell Persistence '. To assess adoptive cell therapy persistence and / or durability, Applicant rechallenged the mice who have completely cleared the tumor. 60 days after the initial primary tumor challenge, these mice were inoculated with 0.5M B16-F10-Ova cells that bear the tumor antigen. Tumor sizes were measured utilizing digital calipers every 2-3 days and calculated the volume using the formula: length x width x [(length x width)0.5] x 7t / 6. Applicant assessed the effects of potency enhancements on tumor control using 2-way ANOVA. Applicant also did endpoint analysis utilizing tumor length or width equal to or greater than 15mm or greater than 50% necrosis of the tumor as clinical endpoints. Survival was measured utilizing Kaplan Meier analysis.

[0218] Antigen Spread'. To assess the ability of these adoptive cell therapies to induce antigen spread, Applicant rechallenged the mice on the opposite flanks with antigen negative tumors, B16-F10 acquired from ATCC and never transduced with a vector expressing ovalbumin. 60 days after the initial primary tumor challenge, these mice were inoculated with 0.1 million B16-F10 cells that do not bear the tumor antigen. Tumor sizes were measured utilizing digital calipers every 2-3 days and calculated the volume using the formula: length x width x [(length x width)0.5] x K / 6. Applicant assessed the effects of potency enhancements on tumor control using 2-way ANOVA. Applicant also did endpoint analysis utilizing tumor length or width equal to or greater than 15 mm or greater than 50% necrosis as clinical endpoints. Survival was measured utilizing Kaplan Meier analysis. Since the transferred cells-49-4927-7786-8905.2Atty. Dkt. No.: 121384-0285 only express OT-I, they are incapable of mediating tumor clearance directly, and antigen spread is inferred.

[0219] Tables 1 -8 shows a summary of the tested gene mutations.

[0220] Variants of interest are those which have a LFC >0 compared to the control. Wildtype proteins of interest are those which have a LFOO compared to the control.

[0221] Variant nomenclature is expanded upon in https: / / atlasgeneticsoncology.org / teaching / 30067 / nomenclature-for-the-description-of- mutations-and-other-sequence-variations, the entire contents of which are incorporated by reference.

[0222] Mutants in bold italic text in the tables were tested in a previous screen.Table 1. Summary of tested gene mutations — TCL Gene variants that increase persistence in the solid tumor microenvironment LFC is log-2 fold change. Positive Ifc (log-2 fold change) indicates higher expression in mutant compared to the controls. Mutants in underlined text are represent variants that are significant in the statistics in Tables 3 and 4 and novel to the screen.-50-4927-7786-8905.2Atty. Dkt. No.: 121384-0285-51-4927-7786-8905.2Atty. Dkt. No.: 121384-0285Table 2. Statistics of tested gene mutations — TCL Gene variants that increase persistence in the solid tumor microenvironment. Statistics of data presented in Table 1.-52-4927-7786-8905.2Aty. Dkt. No.: 121384-02854927-7786-8905.2Atty. Dkt. No.: 121384-0285-54-4927-7786-8905.2Atty. Dkt. No.: 121384-0285Table 3. TCL Genes whose variants increase persistence in the solid tumor microenvironment. Underlined text indicates statistical significance. Presented here are statistics for the negative scores of the mutants.-55-4927-7786-8905.2Atty. Dkt. No.: 121384-0285Table 4. TCL Genes whose variants increase persistence in the solid tumor microenvironment. Positive Ifc (log-2 fold change) indicates higher expression in mutant compared to the controls. Underlined text indicates statistical significance. Presented here are statistics for the positive scores of the mutants.-56-4927-7786-8905.2Atty. Dkt. No.: 121384-0285-57-4927-7786-8905.2Atty. Dkt. No.: 121384-0285Table 5. Summary of tested gene mutations — TCL Gene Variants that increase persistence in the tumor draining lymph nodes. The gene variant lists mutation. Positive Ifc (log-2 fold change) indicates higher expression in mutant compared to the controls. Variants in underlined text are significant and novel to the screen.-58-4927-7786-8905.2Atty. Dkt. No.: 121384-0285-59-4927-7786-8905.2Atty. Dkt. No.: 121384-0285Table 6. Statistics of tested gene mutations — TCL Gene Variants that increase persistence in the tumor draining lymph nodes. The gene variant lists mutation. Positive Ifc (log-2 fold change) indicates higher expression in mutant compared to the controls. Underlined text indicates a mutant with statistical significance. Statistics of data presented in Table 5.-60-4927-7786-8905.2Aty. Dkt. No.: 121384-02854927-7786-8905.2Aty. Dkt. No.: 121384-02854927-7786-8905.2Atty. Dkt. No.: 121384-0285Table 7. TCL Genes whose variants increase persistence in the tumor draining lymph nodes. Id refers to the gene. Num refers to the number of mutations. Presented in Table 7 are negative values (negative score, p-value, fdr, rank, goodsgrna, and Ifc). Positive Ifc (log-2 fold change) indicates higher expression in mutant compared to the controls. Underlined text indicates statistical significance and protein novel to the screen. Presented here are statistics for the negative scores of the mutants.4927-7786-8905.2Atty. Dkt. No.: 121384-0285-64-4927-7786-8905.2Atty. Dkt. No.: 121384-0285Table 8. TCL Genes whose variants increase persistence in the tumor draining lymph nodes. Id refers to the gene. Num refers to the number of mutations. Presented in Table 7 are positive values (negative score, p-value, fdr, rank, goodsgma, and Ifc). Positive Ifc (log-2 fold change) indicates higher expression in mutant compared to the controls. Underlined text indicates statistical significance and protein novel to the screen. Presented here are statistics for the positive scores of the mutants.-65-4927-7786-8905.2Atty. Dkt. No.: 121384-0285-66-4927-7786-8905.2Atty. Dkt. No.: 121384-0285List of Sequences> SEQ ID NO: 1> FAS D265E> Length: 1005 nucleotidesATGCTGGGCATCTGGACCCTCCTACCTCTGGTTCTTACGTCTGTTGCTAGATTATCGTCCAAAAGTGTTAATGCCCAAGTGACTGACATCAACTCCAAGGGATTGGAATTGAGGAAGACTGTTACTACAGTTGAGACTCAGAACTTGGAAGGCCTGCATCATGATGGCCAATTCTGCCATAAGCCCTGTCCTCCAGGTGAAAGGAAAGCTAGGGACTGCACAGTCAATGGGGATGAACCAGACTGCGTGCCCTGCCAAGAAGGGAAGGAGTACACAGACAAAGCCCATTTTTCTTCCAAATGCAGAAGATGTAGATTGTGTGATGAAGGACATGGCTTAGAAGTGGAAATAAACTGCACCCGGACCCAGAATACCAAGTGCAGATGTAAACCAAACTTTTTTTGTAACTCTACTGTATGTGAACACTGTGACCCTTGCACCAAATGTGAACATGGAATCATCAAGGAATGCACACTCACCAGCAACACCAAGTGCAAAGAGGAAGGATCCAGATCTAACTTGGGGTGGCTTTGTCTTCTTCTTTTGCCAATTCCACTAATTGTTTGGGTGAAGAGAAAGGAAGTACAGAAAACATGCAGAAAGCACAGAAAGGAAAACCAAGGTTCTCATGAATCTCCAACTTTAAATCCTGAAACAGTGGCAATAAATTTATCTGATGTTGACTTGAGTAAATATATCACCACTATTGCTGGAGTCATGACACTAAGTCAAGTTAAAGGCTTTGTTCGAAAGAATGGTGTCAATGAAGCCAAAATAGATGAGATCAAGAATGAGAATGTCCAAGACACAGCAGAACAGAAAGTTCAACTGCTTCGTAATTGGCATCAACTTCATGGAAAGAAAGAAGCGTATGACACATTGATTAAAGATCTCAAAAAAGCCAATCTTTGTACTCTTGCAGAGAAAATTCAGACTATCATCCTCAAGGACATTACTAGTGACTCAGAAAATTCAAACTTCAGAAATGAAATCCA AAGCTTGGTC> SEQ ID NO: 2> FYN-TRAF3IP2 Fusion> Length: 2250 nucleotidesATGGGATGTGTGCAGTGTAAAGATAAGGAGGCAACCAAACTGACAGAGGAACGGGATGGCTCCCTGAACCAGTCTTCAGGCTATAGATACGGAACCGACCCAACTCCTCAACACTACCCGTCATTTGGCGTGACTTCTATCCCCAACTACAACAACTTTCACGCAGCCGGGGGGCAGGGACTCACCGTGTTTGGGGGCGTGAACAGTTCTAGCCATACCGGCACACTCCGGACCCGTGGTGGTACAGGTGTCACTCTGTTCGTTGCACTCTACGATTACGAGGCCAGAACGGAAGACGACCTTTCATTCCACAAGGGAGAAAAATTTCAAATTTTAAACTCCTCCGAAGGTGATTGGTGGGAGGCTAGGTCTTTAACCACAGGTGAGACCGGATATATACCCAGCAACTATGTGGCGCCTGTTGATTCCATTCAGGCCGAAGAGTGGTACTTTGGCAAGCTTGGCAGGAAGGATGCTGAGCGACAGCTGTTGTCTTTCGGGAATCCCAGGGGAACATTCCTGATCCGGGAGTCTGAGACCACAAAAGAGACACGGATGAACCGGAGCATCCCTGTCGAGGTGGACGAGTCAGAGCCTTATCCTAGTCAGTTGCTCAAGCCAATTCCAGAGTATTCACCAGAGGAAGAAAGCGAACCACCA-67-4927-7786-8905.2Atty. Dkt. No.: 121384-0285GCTCCAAATATCAGAAACATGGCTCCTAATTCTCTTAGCGCACCCACCATGTTGCACAATAGCAGCGGAGACTTCAGCCAGGCACATAGTACATTGAAGCTGGCAAATCACCAGCGGCCAGTCTCAAGGCAGGTAACCTGCCTGAGAACCCAGGTACTCGAGGATTCCGAAGATTCTTTCTGCAGAAGACATCCCGGCCTGGGTAAAGCTTTCCCAAGTGGATGCTCTGCTGTGAGCGAGCCTGCATCAGAGTCTGTGGTGGGCGCACTGCCTGCCGAGCACCAGTTTTCTTTCATGGAGAAGAGGAATCAATGGCTTGTCAGTCAATTGTCAGCCGCAAGCCCAGACACCGGACACGATAGTGACAAGTCCGATCAGAGTCTCCCTAACGCTAGCGCCGATTCTTTGGGAGGCAGCCAGGAGATGGTGCAGCGACCACAGCCGCACAGGAATCGAGCCGGGCTGGACCTCCCCACGATCGATACGGGCTACGATTCACAGCCACAGGACGTACTCGGTATCAGACAGCTTGAACGCCCACTGCCCTTGACTTCCGTGTGCTACCCTCAGGATCTTCCCAGGCCTCTGCGATCTCGGGAATTCCCTCAGTTCGAGCCCCAAAGATATCCCGCCTGTGCACAGATGTTACCCCCTAACCTGAGTCCTCACGCTCCGTGGAACTATCATTACCACTGTCCCGGTAGCCCTGATCATCAGGTGCCCTATGGTCATGACTACCCCCGGGCAGCTTATCAGCAGGTTATCCAGCCTGCACTGCCCGGCCAACCCCTGCCTGGCGCATCAGTGCGGGGCTTGCACCCCGTGCAGAAGGTTATTCTGAATTATCCTAGCCCCTGGGATCACGAGGAGCGTCCAGCTCAGCGGGATTGTTCCTTCCCAGGGCTTCCGAGACACCAGGACCAGCCACACCATCAACCGCCCAACCGCGCTGGTGCACCAGGGGAGTCATTGGAATGCCCCGCCGAACTCCGCCCTCAGGTTCCGCAGCCACCCTCTCCCGCTGCCGTCCCGAGACCTCCTAGCAATCCACCAGCTAGAGGTACCCTGAAAACATCCAATCTCCCCGAGGAACTGCGGAAGGTCTTCATCACCTACTCTATGGACACGGCTATGGAGGTCGTGAAGTTTGTCAACTTCCTCCTGGTGAACGGTTTTCAGACCGCCATTGACATATTTGAGGACAGGATCAGGGGGATCGACATAATTAAGTGGATGGAAAGATACCTGCGGGACAAGACTGTGATGATTATTGTCGCCATTTCTCCCAAGTACAAACAGGACGTTGAAGGGGCGGAATCCCAGCTTGATGAAGACGAGCACGGCCTGCACACCAAATATATCCACCGGATGATGCAGATCGAATTCATCAAACAAGGATCAATGAACTTCCGGTTTATACCAGTCCTGTTCCCCAATGCCAAGAAGGAGCATGTTCCTACATGGCTGCAGAACACACACGTCTATAGCTGGCCAAAAAACAAAAAGAATATTTTGCTCCGCCTGCTGCGAGAAGAGGAGTACGTGGCTCCACCCCGCGGACCATTACCCACACTCCAGGTGGTGCCTCTG> SEQ ID NO: 3> VAV1-STAP2 Fusion> Length: 2712 nucleotidesATGGAGTTATGGCGACAATGCACACACTGGCTCATTCAATGTAGGGTGCTGCCACCGTCTCATAGAGTCACATGGGACGGTGCCCAAGTTTGTGAGCTCGCCCAAGCCCTTCGGGACGGTGTCCTGCTGTGCCAACTCTTGAATAATCTTCTGCCACATGCTATTAACCTGCGCGAGGTCAACCTTAGGCCCCAAATGTCTCAATTTCTCTGCTTGAAGAATATAAGAACTTTTCTGTCTACCTGTTGTGAGAAATTTGGTCTCAAGCGGTCTGAGCTCTTCGAGGCTTTCGATTTGTTTGACGTTCAGGATTTTGGCAAAGTAATTTATACTTTGAGTGCTTTGAGTTGGACTCCAATTGCTCAAAACCGGGGAATAATGCCATTTCCTACAGAGGAAGAGTCTGTCGGAGACGAGGACATCTATTCTGGGTTAAGTGATCAAATTGACGATACTGTCGAAGAGGATGAAGATCTGTATGACTGCGTTGAAAATGAAGAAGCAGAGGGAGATGAAATTTATGAAGACTTAATGCGCTCTGAGCCAGTTAGTATGCCC-68-4927-7786-8905.2Atty. Dkt. No.: 121384-0285CCAAAGATGACTGAATACGATAAACGGTGCTGCTGCTTACGCGAGATACAACAAACGGAAGAGAAATACACAGACACACTTGGATCCATCCAGCAACATTTCCTGAAACCTCTCCAAAGGTTTCTGAAACCGCAAGATATCGAGATAATCTTCATCAATATAGAGGATCTGCTGAGGGTGCACACTCACTTTCTCAAGGAGATGAAAGAGGCCCTCGGCACTCCTGGAGCTGCAAACTTGTACCAAGTGTTTATAAAATACAAAGAGAGGTTCCTGGTTTACGGCAGGTATTGCTCTCAAGTCGAGTCAGCCAGCAAGCACCTGGATAGGGTTGCCGCAGCACGCGAAGATGTGCAAATGAAGCTTGAAGAATGCTCTCAACGGGCAAATAACGGACGGTTCACCCTTCGTGACTTACTGATGGTTCCGATGCAACGGGTCCTCAAGTACCATCTGCTCCTTCAGGAGCTGGTCAAACATACTCAAGAAGCCATGGAGAAAGAAAATCTCCGACTCGCTCTTGATGCGATGCGAGATCTTGCTCAATGTGTTAACGAGGTCAAAAGAGACAACGAAACCTTGCGGCAAATTACTAATTTCCAACTCTCCATAGAGAACCTGGATCAATCTCTTGCGCATTACGGTCGGCCTAAAATAGACGGGGAACTGAAGATAACATCCGTTGAACGCAGAAGCAAAATGGACAGATACGCGTTTCTTCTGGACAAGGCACTCTTGATCTGCAAACGACGCGGTGACTCATACGACCTTAAGGACTTCGTCAACTTGCATAGTTTCCAAGTGAGAGACGATTCCAGTGGCGATAGAGACAATAAGAAATGGTCCCATATGTTTCTGCTCATTGAAGATCAAGGGGCGCAAGGATACGAACTGTTCTTCAAAACGCGGGAGCTGAAGAAGAAATGGATGGAGCAATTCGAGATGGCCATATCAAACATTTACCCTGAGAATGCCACCGCCAACGGTCACGATTTCCAAATGTTCTCTTTCGAAGAGACTACTTCCTGTAAGGCCTGTCAAATGCTTCTCCGGGGAACCTTCTACCAGGGTTATAGGTGCCACAGGTGCCGGGCATCAGCTCATAAAGAGTGCCTTGGAAGGGTTCCGCCTTGCGGTCGTCACGGGCAAGACTTTCCTGGAACGATGAAGAAAGACAAGTTGCATCGCAGGGCTCAAGACAAGAAACGTAATGAACTGGGACTGCCTAAAATGGAAGTATTTCAAGAATATTATGGCTTACCCCCACCACCCGGAGCAATAGGACCCTTCTTACGCCTTAACCCTGGGGATATTGTGGAACTTACAAAAGCAGAGGCCGAACAGAATTGGTGGGAAGGACGTAATACCTCAACTAATGAGATAGGGTGGTTTCCGTGCAATAGGGTTAAACCTTACGTGCACGGGCCACCGCAGGACCTCAGCGTTCATCTTTGGTATGCGGGACCCATGGAGAGAGCCGGAGCAGAATCCATCCTTGCCAACAGAAGTGACGGTACTTTTCTCGTGCGGCAACGGGTGAAAGATGCCGCTGAATTTGCTATAAGTATAAAGTATAACGTGGAAGTGAAGCACATTAAGATCATGACTGCTGAAGGACTCTATAGGATAACCGAGAAGAAAGCTTTTAGAGGCCTTACCGAGCTTGTGGAATTCTATCAACAAAATTCACTCAAAGACTGTTTCAAGTCCCTCGATACTACACTCCAATTCCCTTTTAAAGAGCCTGAGAAACGCACAATTAGCCGTCCGGCAGGACCCGCGCCCTGTACCGGTGGCCCCAAGCCATTATCTCCTGCGAGTTCCCAAGATAAACTGCCGCCACTGCCCCCTTTACCGAACCAAGAGGAGAATTATGTCACTCCGATCGGCGATGGACCCGCCGTCGATTATGAAAACCAAGACGTGGCCAGCTCATCTTGGCCGGTGATCCTCAAACCTAAGAAACTGCCCAAGCCGCCCGCCAAATTACCCAAACCCCCAGTGGGGCCCAAACCCGAGCCTAAGGTTTTCAACGGTGGACTCGGGCGCAAGTTGCCCGTCAGCAGCGCCCAACCGCTCTTCCCTACAGCAGGTTTGGCCGATATGACCGCTGAACTCCAAAAGAAACTCGAAAAGCGGCGAGCGTTAGAGCAT> SEQ ID NO: 4> IL2RGWT> Length: 1107-69-4927-7786-8905.2Atty. Dkt. No.: 121384-0285ATGTTGAAGCCATCATTACCATTCACATCCCTCTTATTCCTGCAGCTGCCCCTGCTGGGAGTGGGGCTGAACACGACAATTCTGACGCCCAATGGGAATGAAGACACCACAGCTGATTTCTTCCTGACCACTATGCCCACTGACTCCCTCAGTGTTTCCACTCTGCCCCTCCCAGAGGTTCAGTGTTTTGTGTTCAATGTCGAGTACATGAATTGCACTTGGAACAGCAGCTCTGAGCCCCAGCCTACCAACCTCACTCTGCATTATTGGTACAAGAACTCGGATAATGATAAAGTCCAGAAGTGCAGCCACTATCTATTCTCTGAAGAAATCACTTCTGGCTGTCAGTTGCAAAAAAAGGAGATCCACCTCTACCAAACATTTGTTGTTCAGCTCCAGGACCCACGGGAACCCAGGAGACAGGCCACACAGATGCTAAAACTGCAGAATCTGGTGATCCCCTGGGCTCCAGAGAACCTAACACTTCACAAACTGAGTGAATCCCAGCTAGAACTGAACTGGAACAACAGATTCTTGAACCACTGTTTGGAGCACTTGGTGCAGTACCGGACTGACTGGGACCACAGCTGGACTGAACAATCAGTGGATTATAGACATAAGTTCTCCTTGCCTAGTGTGGATGGGCAGAAACGCTACACGTTTCGTGTTCGGAGCCGCTTTAACCCACTCTGTGGAAGTGCTCAGCATTGGAGTGAATGGAGCCACCCAATCCACTGGGGGAGCAATACTTCAAAAGAGAATCCTTTCCTGTTTGCATTGGAAGCCGTGGTTATCTCTGTTGGCTCCATGGGATTGATTATCAGCCTTCTCTGTGTGTATTTCTGGCTGGAACGGACGATGCCCCGAATTCCCACCCTGAAGAACCTAGAGGATCTTGTTACTGAATACCACGGGAACTTTTCGGCCTGGAGTGGTGTGTCTAAGGGACTGGCTGAGAGTCTGCAGCCAGACTACAGTGAACGACTCTGCCTCGTCAGTGAGATTCCCCCAAAAGGAGGGGCCCTTGGGGAGGGGCCTGGGGCCTCCCCATGCAACCAGCATAGCCCCTACTGGGCCCCCCCATGTTACACCCTAAAGCCTGAAACC> SEQ ID NO: 5> IL2RG K315E> Length: 1107ATGTTGAAGCCATCATTACCATTCACATCCCTCTTATTCCTGCAGCTGCCCCTGCTGGGAGTGGGGCTGAACACGACAATTCTGACGCCCAATGGGAATGAAGACACCACAGCTGATTTCTTCCTGACCACTATGCCCACTGACTCCCTCAGTGTTTCCACTCTGCCCCTCCCAGAGGTTCAGTGTTTTGTGTTCAATGTCGAGTACATGAATTGCACTTGGAACAGCAGCTCTGAGCCCCAGCCTACCAACCTCACTCTGCATTATTGGTACAAGAACTCGGATAATGATAAAGTCCAGAAGTGCAGCCACTATCTATTCTCTGAAGAAATCACTTCTGGCTGTCAGTTGCAAAAAAAGGAGATCCACCTCTACCAAACATTTGTTGTTCAGCTCCAGGACCCACGGGAACCCAGGAGACAGGCCACACAGATGCTAAAACTGCAGAATCTGGTGATCCCCTGGGCTCCAGAGAACCTAACACTTCACAAACTGAGTGAATCCCAGCTAGAACTGAACTGGAACAACAGATTCTTGAACCACTGTTTGGAGCACTTGGTGCAGTACCGGACTGACTGGGACCACAGCTGGACTGAACAATCAGTGGATTATAGACATAAGTTCTCCTTGCCTAGTGTGGATGGGCAGAAACGCTACACGTTTCGTGTTCGGAGCCGCTTTAACCCACTCTGTGGAAGTGCTCAGCATTGGAGTGAATGGAGCCACCCAATCCACTGGGGGAGCAATACTTCAAAAGAGAATCCTTTCCTGTTTGCATTGGAAGCCGTGGTTATCTCTGTTGGCTCCATGGGATTGATTATCAGCCTTCTCTGTGTGTATTTCTGGCTGGAACGGACGATGCCCCGAATTCCCACCCTGAAGAACCTAGAGGATCTTGTTACTGAATACCACGGGAACTTTTCGGCCTGGAGTGGTGTGTCTGAGGGACTGGCTGAGAGTCTGCAGCCAGACTACAGTGAACGACTCTGCCTCGTCAGTG-70-4927-7786-8905.2Atty. Dkt. No.: 121384-0285AGATTCCCCCAAAAGGAGGGGCCCTTGGGGAGGGGCCTGGGGCCTCCCCATGCAACCAGCATAGCCCCTACTGGGCCCCCCCATGTTACACCCTAAAGCCTGAAACC> SEQ ID NO: 6> CTNNB1 S45F> Length: 2349ATGGCTACTCAAGCTGATTTGATGGAGTTGGACATGGCCATGGAACCAGACAGAAAAGCGGCTGTTAGTCACTGGCAGCAACAGTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTACCACAGCTCCTTTTCTGAGTGGTAAAGGCAATCCTGAGGAAGAGGATGTGGATACCTCCCAAGTCCTGTATGAGTGGGAACAGGGATTTTCTCAGTCCTTCACTCAAGAACAAGTAGCTGGTAAGAATATTGATGGACAGTATGCAATGACTCGAGCTCAGAGGGTACGAGCTGCTATGTTCCCTGAGACATTAGATGAGGGCATGCAGATCCCATCTACACAGTTTGATGCTGCTCATCCCACTAATGTCCAGCGTTTGGCTGAACCATCACAGATGCTGAAACATGCAGTTGTAAACTTGATTAACTATCAAGATGATGCAGAACTTGCCACACGTGCAATCCCTGAACTGACAAAACTGCTAAATGACGAGGACCAGGTGGTGGTTAATAAGGCTGCAGTTATGGTCCATCAGCTTTCTAAAAAGGAAGCTTCCAGACACGCTATCATGCGTTCTCCTCAGATGGTGTCTGCTATTGTACGTACCATGCAGAATACAAATGATGTAGAAACAGCTCGTTGTACCGCTGGGACCTTGCATAACCTTTCCCATCATCGTGAGGGCTTACTGGCCATCTTTAAGTCTGGAGGCATTCCTGCCCTGGTGAAAATGCTTGGTTCACCAGTGGATTCTGTGTTGTTTTATGCCATTACAACTCTCCACAACCTTTTATTACATCAAGAAGGAGCTAAAATGGCAGTGCGTTTAGCTGGTGGGCTGCAGAAAATGGTTGCCTTGCTCAACAAAACAAATGTTAAATTCTTGGCTATTACGACAGACTGCCTTCAAATTTTAGCTTATGGCAACCAAGAAAGCAAGCTCATCATACTGGCTAGTGGTGGACCCCAAGCTTTAGTAAATATAATGAGGACCTATACTTACGAAAAACTACTGTGGACCACAAGCAGAGTGCTGAAGGTGCTATCTGTCTGCTCTAGTAATAAGCCGGCTATTGTAGAAGCTGGTGGAATGCAAGCTTTAGGACTTCACCTGACAGATCCAAGTCAACGTCTTGTTCAGAACTGTCTTTGGACTCTCAGGAATCTTTCAGATGCTGCAACTAAACAGGAAGGGATGGAAGGTCTCCTTGGGACTCTTGTTCAGCTTCTGGGTTCAGATGATATAAATGTGGTCACCTGTGCAGCTGGAATTCTTTCTAACCTCACTTGCAATAATTATAAGAACAAGATGATGGTCTGCCAAGTGGGTGGTATAGAGGCTCTTGTGCGTACTGTCCTTCGGGCTGGTGACAGGGAAGACATCACTGAGCCTGCCATCTGTGCTCTTCGTCATCTGACCAGCCGACACCAAGAAGCAGAGATGGCCCAGAATGCAGTTCGCCTTCACTATGGACTACCAGTTGTGGTTAAGCTCTTACACCCACCATCCCACTGGCCTCTGATAAAGGCTACTGTTGGATTGATTCGAAATCTTGCCCTTTGTCCCGCAAATCATGCACCTTTGCGTGAGCAGGGTGCCATTCCACGACTAGTTCAGTTGCTTGTTCGTGCACATCAGGATACCCAGCGCCGTACGTCCATGGGTGGGACACAGCAGCAATTTGTGGAGGGGGTCCGCATGGAAGAAATAGTTGAAGGTTGTACCGGAGCCCTTCACATCCTAGCTCGGGATGTTCACAACCGAATTGTTATCAGAGGACTAAATACCATTCCATTGTTTGTGCAGCTGCTTTATTCTCCCATTGAAAACATCCAAAGAGTAGCTGCAGGGGTCCTCTGTGAACTTGCTCAGGACAAGGAAGCTGCAGAAGCTATTGAAGCTGAGGGAGCCACAGCTCCTCTGACAGAGTTACTTCACTCTAGGAATGAAGGTGTGGCGACATATGCAGCTGCTGTTTTGTTCCGAATGTCTGAGGACAAGCCACAAGATTACAAGAAACGGCTTTCAGTTGAGCTGACCAGCTCTCTCTTCAGAACAGA-71-4927-7786-8905.2Atty. Dkt. No.: 121384-0285GCCAATGGCTTGGAATGAGACTGCTGATCTTGGACTTGATATTGGTGCCCAGGGAGAACCCCTTGGATATCGCCAGGATGATCCTAGCTATCGTTCTTTTCACTCTGGTGGATATGGCCAGGATGCCTTGGGTATGGACCCCATGATGGAACATGAGATGGGTGGCCACCACCCTGGTGCTGACTATCCAGTTGATGGGCTGCCAGATCTGGGGCATGCCCAGGACCTCATGGATGGGCTGCCTCCAGGTGACAGCAATCAGCTGGCCTGGTTTGATA CTGACCTG> SEQ ID NO: 7> CAPRIN-JAK2 Fusion> Length: 2964ATGCCATCAGCCACTTCTCACTCCGGTTCTGGGTCCAAAAGCTCTGGACCACCTCCTCCAAGCGGCAGTTCTGGCAGTGAGGCCGCAGCAGGAGCGGGTGCTGCTGCCCCTGCATCTCAGCATCCGGCGACCGGAACCGGAGCAGTTCAGACGGAAGCTATGAAGCAGATTTTAGGCGTAATTGACAAGAAGCTGAGGAACCTCGAGAAGAAGAAAGGAAAACTGGACGATTACCAGGAGAGGATGAATAAGGGCGAAAGGCTGAACCAGGACCAGTTAGATGCTGTCTCCAAATATCAAGAGGTAACTAATAATTTGGAGTTCGCTAAGGAACTCCAGCGGAGTTTTATGGCTCTCTCACAGGATATCCAGAAAACAATCAAGAAGACTGCCCGCCGAGAGCAATTGATGCGAGAAGAGGCAGAGCAGAAACGACTGAAAACCGTTTTGGAACTGCAGTACGTTCTGGACAAATTAGGAGATGATGAGGTCAGAACCGATCTGAAGCAGGGCCTTAATGGCGTACCTATCCTGTCTGAGGAAGAACTGTCCTTGTTAGATGAGTTTTATAAACTTGTAGATCCAGAGAGGGATATGAGTCTTAGACTGAACGAACAGTATGAGCATGCCAGCATCCACCTTTGGGACTTACTGGAAGGAAAAGAGAAACCTGTATGCGGGACTACTTACAAAGTGTTAAAAGAGATAGTGGAACGAGTATTCCAGTCTAATTACTTCGATTCTACTCACAATCACCAGAATGGCCTGTGTGAGGAAGAGGAAGCCGCCAGTGCGCCCGCTGTGGAAGACCAGGTACCAGAAGCTGAACCGGAACCTGCTGAAGAGTATACCGAGCAGTCTGAAGTCGAGTCAACTGAGTATGTGAACCGTCAGTTCATGGCAGAAACTCAGTTCACATCAGGCGAAAAGGAGCAGGTTGACGAATGGACAGTGGAGACGGTGGAAGTGGTTAATTCTCTTCAGCAGCAGCCACAAGCTGCCTCTCCCAGTGTACCGGAGCCCCACAGTCTTACACCCGTCGCTCAGGCTGACCCCTTGGTGAGACGCCAGCGCGTGCAGGATCTGATGGCTCAGATGCAGGGCCCCTACAATTTTATCCAGGATAGCATGCTTGATTTCGAGAACCAGACACTTGACCCTGCTATCGTCTCTGCCCAACCAATGAACCCAACACAAAATATGGACATGCCCCAACTCGTGTGTCCACCTGTGCATAGTGAGAGCAGGTTAGCACAACCAAATCAGGTTCCAGTTCAGCCTGAGGCAACGCAAGTTCCACTTGTCAGCAGTACCAGCGAGGGCTACACTGCTTCCCAGCCCCTGTACCAGCCCAGTCACGCCACAGAGCAGAGACCCCAGAAAGAGCCAATCGACCAGATCCAAGCAACCATCTCCCTGAACACAGACCAGACCACAGCTTCATCTAGCCTGCCCGCCGCCAGCCAGCCCCAAGTCTTTCAGGCAGGCACGTCTAAACCACTTCATTCTTCTGGGATAAACGTTAATGCCGCCCCTTTCCAGTCTATGCAGACGGTCTTCAACATGAATGCGCCTGTGCCCCCGGTAAACGAGCCTGAGACTCTGAAGCAGCAAAATCAGTACCAGGCGTCCTACAATCAAAGTTTCTCATCCCAGCCCCACCAAGTCGAGCAGACAGAGCTGCAGCAGGAGCAGCTTCAAACTCTGCAAGAGCGGATCCCTTGGGTGCCCCCTGAATGTATAGAGAATCCGAAGAATCTGAATCTCGCCACCGACAAGTGGTCCTTTGGCACCACCTTATGGGAGATCTGTAGCGG-72-4927-7786-8905.2Atty. Dkt. No.: 121384-0285CGGTGATAAACCGTTGAGCGCTTTAGATTCACAAAGGAAGTTACAATTTTATGAGGACCGTCACCAACTCCCCGCCCCCAAGTGGGCAGAGCTCGCCAATCTTATCAACAATTGCATGGATTATGAGCCCGATTTTAGGCCATCATTTAGGGCTATCATTAGAGACCTGAATAGCTTATTTACACCTGACTATGAGCTCCTGACAGAGAATGATATGCTCCCCAACATGCGCATCGGTGCACTGGGTTTCTCCGGCGCCTTCGAGGACCGCGACCCTACACAGTTTGAAGAGAGGCACCTCAAGTTTCTGCAGCAGCTTGGCAAGGGGAACTTTGGGAGTGTCGAGATGTGCCGGTACGATCCATTACAAGACAATACAGGAGAGGTTGTAGCCGTCAAGAAGCTCCAGCACAGCACGGAAGAACACCTGAGAGATTTTGAGAGAGAGATCGAAATCCTCAAGAGCTTGCAGCACGACAACATTGTTAAGTACAAAGGAGTGTGTTACAGTGCGGGGCGCAGAAATTTGAAGCTCATAATGGAATATCTCCCCTACGGTTCCCTGCGCGATTACCTTCAGAAACACAAGGAGAGGATAGACCACATTAAACTGCTGCAGTATACTTCTCAGATATGTAAGGGCATGGAGTATCTGGGAACTAAACGCTACATCCACCGCGACCTTGCAACTCGGAACATCCTCGTCGAAAACGAAAACAGGGTTAAGATCGGCGATTTTGGTTTAACAAAGGTTCTCCCGCAAGACAAAGAGTATTACAAAGTTAAAGAGCCTGGGGAAAGTCCAATTTTCTGGTATGCCCCAGAGTCCCTTACTGAGAGTAAGTTCAGTGTTGCTTCCGATGTGTGGTCATTCGGTGTGGTGCTGTACGAGCTCTTTACATATATCGAAAAGAGCAAGTCACCACCCGCGGAATTCATGCGGATGATAGGCAACGACAAACAGGGGCAGATGATTGTGTTCCACCTGATCGAACTCCTGAAGAATAACGGTAGGTTGCCCAGACCCGACGGATGCCCGGACGAAATATACATGATCATGACCGAATGTTGGAATAACAACGTGAACCAGAGACCATCTTTCCGAGATCTTGCCCTGAGAGTAGACCAGATTAGAGACAATATGGCG> SEQ ID NO: 8> mCTLA4-mCD28 Fusion> Length: 693ATGGCCTGTCTAGGACTACGAAGATATAAGGCACAACTGCAATTGCCTTCCAGAACATGGCCATTCGTCGCACTCCTCACTCTTCTGTTCATCCCTGTTTTCTCAGAAGCGATTCAGGTCACCCAACCCTCTGTCGTTTTGGCTTCAAGCCACGGTGTCGCTAGTTTTCCATGCGAGTACAGCCCAAGTCATAATACTGACGAGGTGCGTGTGACAGTGCTGAGGCAAACGAACGATCAAATGACCGAAGTCTGCGCTACTACTTTTACCGAAAAGAATACGGTAGGTTTTCTGGACTATCCTTTCTGCTCTGGTACATTTAATGAGAGCAGGGTCAACCTAACTATACAAGGCCTACGCGCAGTCGATACTGGCCTTTATCTCTGTAAAGTAGAGCTCATGTACCCACCACCCTATTTTGTGGGAATGGGGAATGGCACACAAATTTATGTGATTGATCCAGAACCATGCCCAGATAGCGATTTTCTACTTTGGATTCTCGTCGCGGTCAGTCTAGGTCTGTTCTTCTACTCCTTTCTGGTCAGTGCGGTAAGTCTGAGCAAAATGACAAACAGCCGGAGAAACAGGTTGCTTCAGTCCGATTATATGAATATGACACCTCGCCGGCCCGGCCTGACGCGAAAACCTTATCAGCCCTACGCTCCTGCCAGGGATTTCGCTGCGTATCGGCCT> SEQ ID NO: 9-73-4927-7786-8905.2Atty. Dkt. No.: 121384-0285> IKZF2-ERBB4 Fusion> Length: 3876ATGGAAACAGAAGCGATCGATGGGTATATCACTGTTTGCGCAGGGACAGAAAATA AACTTAGCTCCCTCTCAGACCTTGAGCAACAATATCGAGCTTTAAGGAAGTACTAT GAGAATTGCGAGGTGGTGATGGGTAACCTCGAGATCACCTCAATTGAACATAATCG CGATTTATCCTTTCTCCGTTCCGTCCGTGAAGTCACCGGATATGTGCTGGTCGCCCT GAACCAATTTCGATACCTGCCATTGGAGAATCTGCGGATTATCCGGGGCACGAAAC TGTATGAAGACAGGTACGCCCTTGCAATTTTCTTAAATTACCGGAAAGACGGAAAT TTCGGACTTCAGGAATTAGGCCTTAAGAACCTTACAGAGATACTCAACGGCGGAG TCTACGTAGATCAAAATAAATTTCTTTGCTACGCAGACACAATTCACTGGCAAGAT ATCGTAAGGAACCCATGGCCTTCCAATTTGACCTTGGTGAGTACCAACGGGAGCT CAGGATGTGGCAGGTGTCATAAATCATGCACCGGGCGATGTTGGGGCCCCACAGA GAATCATTGCCAAACCCTGACCCGCACCGTGTGCGCCGAACAATGTGATGGTCGA TGTTACGGACCATACGTCAGTGACTGCTGTCACCGGGAGTGTGCAGGCGGCTGCA GCGGCCCTAAAGATACTGACTGCTTCGCTTGCATGAACTTCAACGACTCAGGTGC ATGTGTGACACAATGTCCACAAACTTTCGTCTACAATCCAACCACATTCCAATTGG AGCATAACTTTAACGCGAAGTATACCTACGGGGCATTTTGCGTCAAGAAATGTCCGCACAACTTTGTCGTAGACTCTTCCAGCTGCGTTCGTGCTTGTCCCAGCTCAAAGAT GGAAGTTGAAGAAAATGGAATAAAGATGTGTAAACCGTGCACGGACATCTGCCCA AAGGCATGCGATGGCATAGGAACAGGGTCCTTGATGTCAGCGCAAACGGTAGATT CTTCTAATATAGATAAGTTTATTAACTGTACCAAGATTAACGGGAACCTCATTTTCC TTGTGACTGGAATTCATGGCGACCCTTATAATGCCATTGAGGCGATTGACCCGGAG AAATTGAACGTTTTCAGGACTGTCCGTGAGATAACCGGATTCCTCAACATTCAATC CTGGCCCCCAAATATGACTGATTTCTCTGTCTTTTCCAATCTTGTGACCATTGGTGG TAGGGTTCTGTATTCCGGACTGTCCTTGCTGATTCTCAAGCAGCAAGGCATTACCT CTCTTCAATTTCAAAGCCTGAAAGAGATCAGCGCGGGCAACATCTACATCACCGAT AACAGCAACCTCTGTTATTATCATACCATTAATTGGACCACACTGTTTTCTACAATA AATCAAAGGATAGTTATCCGGGACAATCGAAAGGCAGAAAACTGTACGGCTGAGG GGATGGTATGCAACCATCTGTGTAGTTCTGACGGGTGTTGGGGACCAGGCCCCGAT CAGTGCCTCTCTTGTCGCCGGTTCTCCAGGGGACGAATCTGTATTGAGTCATGTAA CCTGTATGATGGTGAATTCAGGGAATTCGAGAATGGATCAATCTGTGTGGAGTGTG ACCCACAATGTGAGAAAATGGAAGACGGACTGCTCACCTGCCACGGGCCTGGTCCTGATAATTGTACTAAATGTTCACATTTTAAGGATGGCCCAAATTGCGTGGAGAAA TGTCCAGATGGACTGCAAGGGGCGAACAGTTTTATCTTTAAATATGCCGACCCAGA CCGGGAGTGTCACCCCTGCCACCCAAATTGTACACAGGGCTGCAACGGTCCTACT AGCCATGACTGTATTTACTATCCTTGGACAGGGCATTCTACCCTGCCCCAACACGC ACGGACGCCCCTGATTGCTGCAGGCGTCATTGGTGGCCTCTTCATCCTCGTTATAG TGGGCCTGACTTTCGCAGTTTATGTCCGGCGTAAATCCATTAAGAAGAAGCGCGCG CTGAGACGGTTTCTCGAGACTGAACTGGTCGAACCCTTGACCCCATCTGGGACAG CCCCAAACCAAGCCCAACTTCGCATTTTGAAAGAAACCGAATTAAAACGCGTCAA AGTTCTGGGGAGCGGAGCCTTCGGCACTGTCTATAAAGGGATATGGGTGCCGGAA GGGGAAACAGTTAAGATTCCCGTGGCTATCAAAATCTTGAACGAGACTACTGGTC CAAAGGCTAATGTAGAATTCATGGATGAAGCATTGATCATGGCTTCTATGGACCATC CTCACCTGGTGAGATTGCTGGGCGTTTGTCTGAGTCCGACTATTCAGCTGGTGACA CAATTGATGCCACATGGCTGCCTTCTGGAATATGTACACGAACACAAAGACAATAT-74-4927-7786-8905.2Atty. Dkt. No.: 121384-0285CGGCAGCCAACTGCTGCTGAATTGGTGCGTCCAGATTGCGAAAGGCATGATGTATCTCGAGGAACGCAGGTTGGTGCACCGCGATCTTGCGGCGCGCAATGTCCTCGTTAAATCCCCAAACCATGTGAAAATAACTGATTTTGGCTTGGCCAGGCTCCTGGAAGGTGATGAAAAGGAGTACAACGCAGATGGTGGCAAAATGCCAATAAAATGGATGGCATTGGAATGTATCCACTATAGAAAGTTCACGCATCAAAGCGACGTTTGGAGCTACGGCGTTACCATTTGGGAATTGATGACATTCGGCGGAAAACCCTATGATGGAATCCCGACCCGTGAAATACCCGATCTGTTGGAAAAGGGCGAGCGGTTGCCACAACCCCCGATATGCACTATAGATGTCTATATGGTCATGGTTAAGTGCTGGATGATTGACGCCGACTCTCGACCCAAATTCAAGGAGCTGGCGGCTGAGTTTTCCAGAATGGCACGGGATCCACAACGATATCTTGTGATACAAGGTGACGATCGCATGAAGCTCCCCTCACCTAACGACTCCAAATTCTTTCAGAACCTTCTGGACGAAGAGGACCTCGAAGACATGATGGATGCAGAAGAATATCTGGTCCCTCAAGCTTTCAATATCCCACCCCCAATTTATACCTCACGCGCGAGAATTGATTCTAACCGCAGCGAAATCGGCCATTCACCCCCACCTGCGTATACTCCTATGAGCGGGAATCAATTTGTGTACCGGGATGGTGGGTTTGCCGCGGAGCAAGGAGTGAGCGTGCCATATCGGGCCCCCACTTCAACAATTCCTGAAGCCCCGGTGGCTCAAGGGGCAACGGCCGAGATCTTTGATGATTCCTGCTGCAACGGAACACTGCGTAAACCTGTCGCCCCGCATGTGCAGGAAGATAGCTCTACACAGAGGTATTCCGCCGACCCGACTGTATTTGCCCCCGAACGATCACCCCGCGGCGAGCTTGATGAGGAAGGCTATATGACTCCTATGCGTGATAAACCAAAACAAGAGTATTTGAACCCCGTGGAAGAAAATCCTTTTGTCAGTAGAAGAAAGAATGGGGACTTACAAGCGCTGGATAATCCAGAATATCACAACGCCAGTAACGGGCCCCCAAAAGCGGAAGATGAATACGTAAACGAACCCCTGTATCTTAATACCTTTGCCAACACTCTTGGTAAAGCTGAATACCTGAAGAACAATATACTTTCTATGCCGGAGAAGGCTAAGAAGGCGTTTGATAACCCGGATTACTGGAATCACTCTTTACCCCCACGCTCTACGCTGCAACATCCCGATTACCTGCAGGAATACTCTACTAAGTATTTCTATAAACAGAACGGAAGGATCCGCCCGATTGTAGCTGAAAACCCTGAGTACTTAAGTGAATTCAGCCTTAAACCCGGGACAGTGCTGCCCCCACCACCATACAGACATCGTAACACGGTTGTT> SEQ ID NO: 10> PABPC1-TYK2 Fusion> Length: 2151ATGAATCCCTCTGCACCATCATATCCGATGGCCAGCCTCTACGTGGGTGATCTGCACCCTGACGTGACCGAAGCAATGCTCTATGAGAAATTCAGCCCTGCAGGGCCTATCCTTTCCATCCGCGTGTGTAGAGATATGATCACAAGGCGGAGCCTGGGCTACGCATATGTGAATTTTCAACAGCCCGCGGACGCCGAGAGAGCTTTAGATACAATGAACTTTGACGTCATTAAGGGTAAACCTGTTAGGATCATGTGGTCACAACGTGACCCCTCATTGCGAAAATCAGGTGTGGGAAATATTTTTATCAAAAATCTTGATAAGAGCATCGACAACAAGGCCCTCTATGATACATTTTCCGCCTTCGGGAATATACTGAGCTGCAAGGTAGTTTGTGACGAGAATGGTAGCAAAGGATACGGGTTTGTGCACTTCGAAACCCAAGAGGCAGCCGAACGGGCCATCGAAAAAATGAATGGTATGCTCTTGAACGACCGCAAGGTGTTCGTCGGACGGTTCAAAAGCAGAAAAGAGAGGGAAGCTGAACTTGGAGCCAGGGCGAAGGAATTTACGAATGTGTATATAAAGAATTTCGGCGAGGACATGGATGATGAACGCTTAAAGGACCTGTTCGGGAAATTCGGACCGGCCCTCAGCGTGAAGGTGAT-75-4927-7786-8905.2Atty. Dkt. No.: 121384-0285GACCGACGAATCTGGCAAGTCAAAAGGATTCGGCTTCGTGAGTTTTGAACGGCACGAGGATGCCCAGAAGGCCGTGGATGAAATGAATGGGAAAGAGCTGAATGGAAAACAAATTTATGTGGGAAGAGCCCAGAAAAAGGTAGAGAGACAAACTGAGCTCAAGCGCAAATTTGAACAAATGAAACAGGATCGTATCACCCGCTACCAGGGCGTCAATCTGTACGTCAAAAACCTGGACGATGGTATTGACGACGAGCGCCTGCGAAAGGAATTCAGTCCCTTCGGAACTATTACAAGCGCAAAAATGGACAAATGGGGCTTTGGAGCCACCCTGCTTGAAATCTGCTTTGACGGGGAGGCTCCTCTTCAGAGTCGTTCACCATCCGAAAAGGAACACTTCTATCAGCGTCAGCACAGACTGCCTGAACCTTCATGCCCTCAGCTGGCGACTCTGACGTCACAGTGCCTGACCTATGAGCCAACTCAGCGACCTTCATTCCGCACTATCCTGCGCGACTTAACCCGGCTGCAGCCTCACAATCTCGCCGATGTGCTCACAGTAAACCCTGATAGTCCCGCATCTGATCCTACGGTGTTCCACAAAAGATACCTCAAAAAAATCCGGGATTTGGGGGAGGGGCATTTCGGCAAAGTGTCTCTTTATTGCTACGATCCAACTAATGACGGAACGGGAGAGATGGTCGCCGTGAAAGCATTGAAGGCAGATTGTGGACCTCAGCACCGAAGTGGTTGGAAACAGGAAATTGACATTCTCAGAACACTCTATCACGAACATATTATCAAGTACAAGGGCTGCTGCGAAGATCAAGGGGAAAAATCACTCCAACTCGTCATGGAGTATGTACCTCTGGGCAGTCTGCGCGACTATCTTCCCAGACATTCTATAGGGCTGGCTCAGCTGTTGCTGTTTGCACAGCAAATTTGTGAGGGGATGGCGTATTTACATGCACAGCACTACATACACAGGGACCTGGCAGCCAGAAACGTGCTGCTCGATAACGACAGACTCGTGAAAATCGGCGACTTTGGCTTGGCTAAGGCGGTGCCTGAGGGGCACGAATACTACCGAGTCCGGGAGGATGGCGATTCTCCGGTTTTCTGGTACGCGCCCGAATGCCTCAAGGAGTACAAATTCTACTATGCCTCAGATGTGTGGTCTTTTGGCGTAACGCTCTACGAACTGCTGACCCACTGTGATTCATCACAGTCCCCTCCTACCAAGTTTCTTGAACTGATCGGAATTGCCCAGGGTCAGATGACCGTACTCCGACTGACTGAACTTCTGGAAAGAGGCGAGCGACTGCCACGGCCGGACAAGTGTCCATGCGAGGTCTACCATTTGATGAAGAATTGTTGGGAGACCGAAGCATCATTTAGACCAACTTTCGAGAATCTCATCCCGATTTTAAAGACCGTGCATGAAAAATATCAGGGCCAGGCTCCCAGCGTATTTTCCGTATGCSEQ ID NO: 11> IL7R T244I245CPT> Length: 1386ATGACAATTCTCGGAACAACCTTTGGCATGGTGTTTAGCCTGCTTCAAGTCGTGAGCGGGGAGAGCGGGTACGCTCAGAACGGGGACCTGGAGGACGCCGAACTTGACGACTACTCCTTCTCATGTTATTCACAGCTGGAGGTGAATGGAAGCCAACACAGCTTAACATGTGCATTCGAGGATCCCGACGTGAATATAACAAATCTGGAGTTTGAAATATGCGGGGCATTGGTAGAGGTAAAGTGCCTGAACTTCAGAAAACTCCAGGAGATCTACTTTATTGAGACAAAAAAATTCCTGCTTATTGGCAAAAGTAATATATGCGTAAAGGTCGGAGAAAAATCTCTGACATGTAAAAAAATTGACTTGACCACTATCGTGAAACCTGAGGCTCCCTTCGATCTGTCAGTAGTATATAGGGAAGGAGCCAATGACTTCGTCGTAACATTCAACACATCCCACTTACAGAAGAAATACGTGAAGGTGTTGATGCATGACGTCGCCTATCGGCAGGAGAAAGATGAGAACAAGTGGACCCATGTGAATTTGTCTAGCACTAAGCTGACTTTACTCCAAAGAAAGCTGCAGCCCGCTGCCATGTACGAGATTAAGGTTCGCAGTATCCCCGACCATTATTTCAAAGGTTTCTGGAGTGAGTGGAGTC-76-4927-7786-8905.2Atty. Dkt. No.: 121384-0285CTAGTTATTACTTTCGCACTCCCGAGATAAATAATTCCAGCGGCGAGATGGATCCAATCTTGCTGATCTGTCCTACCATCAGTATTTTGTCCTTTTTCTCAGTGGCTCTGCTGGTGATTCTGGCGTGCGTTCTGTGGAAGAAGCGAATCAAACCCATCGTGTGGCCCTCCCTCCCTGATCACAAAAAAACCCTGGAACACCTGTGCAAAAAGCCACGCAAAAATTTGAATGTGAGTTTCAATCCAGAATCATTCCTGGACTGCCAGATACATAGGGTCGATGATATTCAGGCAAGAGATGAAGTAGAAGGCTTCCTTCAGGATACATTTCCTCAGCAATTGGAGGAGTCTGAAAAGCAGCGACTCGGCGGAGACGTGCAGTCACCCAACTGCCCATCTGAAGATGTGGTCATCACCCCTGAGTCCTTTGGGCGGGACTCCAGTTTAACATGTCTTGCCGGAAACGTATCCGCATGCGACGCCCCAATCCTCAGCAGTTCACGCTCCCTGGATTGCCGTGAGAGCGGAAAAAATGGTCCTCATGTCTACCAGGACCTCCTGTTGTCCCTGGGTACAACCAACTCTACCCTCCCCCCCCCATTTAGCCTGCAGTCAGGAATACTGACATTGAACCCAGTCGCCCAAGGCCAGCCTATTTTGACTTCACTGGGATCCAACCAGGAGGAGGCCTACGTGACCATGTCCAGCTTCTATCAGAACCAGSEQ ID NO: 12> mCD3E S34C> Length: 567ATGCGATGGAACACATTCTGGGGAATCTTGTGCTTATCATTACTGGCCGTAGGAAC CTGCCAGGATGACGCAGAGAACATAGAATACAAGGTGTCTATATGTGGGACATCTG TGGAGTTAACTTGCCCTCTTGATAGTGACGAAAATCTCAAGTGGGAGAAGAATGG ACAGGAATTGCCGCAGAAACATGACAAGCACCTGGTGCTCCAGGACTTTAGCGAGGTTGAGGATAGTGGGTATTACGTGTGCTACACACCCGCCAGTAACAAGAATACTT ATCTGTACTTAAAAGCTAGGGTGTGTGAATACTGCGTTGAGGTCGATCTGACGGCG GTGGCCATCATAATAATTGTCGACATTTGCATTACGCTGGGGTTGTTAATGGTGATT TATTACTGGTCCAAGAACCGTAAAGCAAAAGCTAAGCCTGTTACCAGGGGCACCGGCGCTGGATCCAGACCGCGAGGACAGAACAAAGAGAGGCCCCCACCAGTCCCAA ACCCTGATTACGAACCCATTAGGAAGGGACAGAGGGATCTGTATTCTGGCCTTAAC CAAAGGGCAGTG> SEQ ID NO: 13> TRAF3 S359R> Length: 1458ATGGAGTCGAGTAAAAAGATGGACTCTCCTGGCGCGCTGCAGACTAACCCGCCGCTAAAGCTGCACACTGACCGCAGTGCTGGGACGCCAGTTTTTGTCCCTGAACAAGGAGGTTACAAGGAAAAGTTTGTGAAGACCGTGGAGGACAAGTACAAGTGTGAGAAGTGCCACCTGGTGCTGTGCAGCCCGAAGCAGACCGAGTGTGGGCACCGCTTCTGCGAGAGCTGCATGGCGGCCCTGCTGAGCTCTTCAAGTCCAAAATGTACAGCGTGTCAAGAGAGCATCGTTAAAGATAAGGTGTTTAAGGATAATTGCTGCAAGAGAGAAAT-77-4927-7786-8905.2Atty. Dkt. No.: 121384-0285TCTGGCTCTTCAGATCTATTGTCGGAATGAAAGCAGAGGTTGTGCAGAGCAGTTAATGCTGGGACATCTGCTGGTGCATTTAAAAAATGATTGCCATTTTGAAGAACTTCCATGTGTGCGTCCTGACTGCAAAGAAAAGGTCTTGAGGAAAGACCTGCGAGACCACGTGGAGAAGGCGTGTAAATACCGGGAAGCCACATGCAGCCACTGCAAGAGTCAGGTTCCGATGATCGCGCTGCAGGTTTCCTTGTTGCAGAATGAAAGTGTAGAAAAAAACAAGAGCATACAAAGTTTGCACAATCAGATATGTAGCTTTGAAATTGAAATTGAGAGACAAAAGGAAATGCTTCGAAATAATGAATCCAAAATCCTTCATTTACAGCGAGTGATAGACAGCCAAGCAGAGAAACTGAAGGAGCTTGACAAGGAGATCCGGCCCTTCCGGCAGAACTGGGAGGAAGCAGACAGCATGAAGAGCAGCGTGGAGTCCCTCCAGAACCGCGTGACCGAGCTGGAGAGCGTGGACAAGAGCGCGGGGCAAGTGGCTCGGAACACAGGCCTGCTGGAGTCCCAGCTGAGCCGGCATGACCAGATGCTGAGTGTGCACGACATCCGCCTAGCCGACATGGACCTGCGCTTCCAGGTCCTGGAGACCGCCAGCTACAATGGAGTGCTCATCTGGAAGATTCGCGACTACAAGCGGCGGAAGCAGGAGGCCGTCATGGGGAAGACCCTGTCCCTTTACAGGCAGCCTTTCTACACTGGTTACTTTGGCTATAAGATGTGTGCCAGGGTCTACCTGAACGGGGACGGGATGGGGAAGGGGACGCACTTGTCGCTGTTTTTTGTCATCATGCGTGGAGAATATGATGCCCTGCTTCCTTGGCCGTTTAAGCAGAAAGTGACACTCATGCTGATGGATCAGGGGTCCTCTCGACGTCATTTGGGAGATGCATTCAAGCCCGACCCCAACAGCAGCAGCTTCAAGAAGCCCACTGGAGAGATGAATATCGCCTCTGGCTGCCCAGTCTTTGTGGCCCAAACTGTTCTAGAAAATGGGACATATATTAAAGATGATACAATTTTTATTAAAGTCATAGTGGATACTTCGGATCTGCCCGATCCCTGA> SEQ ID NO: 14> IDH1 R132C> Length: 1242ATGTCCAAAAAAATCAGTGGCGGTTCTGTGGTAGAGATGCAAGGAGATGAAATGACACGAATCATTTGGGAATTGATTAAAGAGAAACTCATTTTTCCCTACGTGGAATTGGATCTACATAGCTATGATTTAGGCATAGAGAATCGTGATGCCACCAACGACCAAGTCACCAAGGATGCTGCAGAAGCTATAAAGAAGCATAATGTTGGCGTCAAATGTGCCACTATCACTCCTGATGAGAAGAGGGTTGAGGAGTTCAAGTTGAAACAAATGTGGAAATCACCAAATGGCACCATACGAAATATTCTGGGTGGCACGGTCTTCAGAGAAGCCATTATCTGCAAAAATATCCCCCGGCTTGTGAGTGGATGGGTAAAACCTATCATCATAGGTTGTCATGCTTATGGGGATCAATACAGAGCAACTGATTTTGTTGTTCCTGGGCCTGGAAAAGTAGAGATAACCTACACACCAAGTGACGGAACCCAAAAGGTGACATACCTGGTACATAACTTTGAAGAAGGTGGTGGTGTTGCCATGGGGATGTATAATCAAGATAAGTCAATTGAAGATTTTGCACACAGTTCCTTCCAAATGGCTCTGTCTAAGGGTTGGCCTTTGTATCTGAGCACCAAAAACACTATTCTGAAGAAATATGATGGGCGTTTTAAAGACATCTTTCAGGAGATATATGACAAGCAGTACAAGTCCCAGTTTGAAGCTCAAAAGATCTGGTATGAGCATAGGCTCATCGACGACATGGTGGCCCAAGCTATGAAATCAGAGGGAGGCTTCATCTGGGCCTGTAAAAACTATGATGGTGACGTGCAGTCGGACTCTGTGGCCCAAGGGTATGGCTCTCTCGGCATGATGACCAGCGTGCTGGTTTGTCCAGATGGCAAGACAGTAGAAGCAGAGGCTGCCCACGGGACTGTAACCCGTCACTACCGCATGTACCAGAAAGGACAGGAGACGTCCACCAATCCCATTGCTTCCATT-78-4927-7786-8905.2Atty. Dkt. No.: 121384-0285TTTGCCTGGACCAGAGGGTTAGCCCACAGAGCAAAGCTTGATAACAATAAAGAGCTTGCCTTCTTTGCAAATGCTTTGGAAGAAGTCTCTATTGAGACAATTGAGGCTGGCTTCATGACCAAGGACTTGGCTGCTTGCATTAAAGGTTTACCCAATGTGCAACGTTCTGACTACTTGAATACATTTGAGTTCATGGATAAACTTGGAGAAAACTTGAAGATCAAACTAGCTCAGGCCAAACTT> SEQ ID NO: 15> AKT1 WT> Length: 1440ATGAGCGACGTGGCTATTGTGAAGGAGGGTTGGCTGCACAAACGAGGGGAGTACATCAAGACCTGGCGGCCACGCTACTTCCTCCTCAAGAATGATGGCACCTTCATTGGCTACAAGGAGCGGCCGCAGGATGTGGACCAACGTGAGGCTCCCCTCAACAACTTCTCTGTGGCGCAGTGCCAGCTGATGAAGACGGAGCGGCCCCGGCCCAACACCTTCATCATCCGCTGCCTGCAGTGGACCACTGTCATCGAACGCACCTTCCATGTGGAGACTCCTGAGGAGCGGGAGGAGTGGACAACCGCCATCCAGACTGTGGCTGACGGCCTCAAGAAGCAGGAGGAGGAGGAGATGGACTTCCGGTCGGGCTCACCCAGTGACAACTCAGGGGCTGAAGAGATGGAGGTGTCCCTGGCCAAGCCCAAGCACCGCGTGACCATGAACGAGTTTGAGTACCTGAAGCTGCTGGGCAAGGGCACTTTCGGCAAGGTGATCCTGGTGAAGGAGAAGGCCACAGGCCGCTACTACGCCATGAAGATCCTCAAGAAGGAAGTCATCGTGGCCAAGGACGAGGTGGCCCACACACTCACCGAGAACCGCGTCCTGCAGAACTCCAGGCACCCCTTCCTCACAGCCCTGAAGTACTCTTTCCAGACCCACGACCGCCTCTGCTTTGTCATGGAGTACGCCAACGGGGGCGAGCTGTTCTTCCACCTGTCCCGGGAGCGTGTGTTCTCCGAGGACCGGGCCCGCTTCTATGGCGCTGAGATTGTGTCAGCCCTGGACTACCTGCACTCGGAGAAGAACGTGGTGTACCGGGACCTCAAGCTGGAGAACCTCATGCTGGACAAGGACGGGCACATTAAGATCACAGACTTCGGGCTGTGCAAGGAGGGGATCAAGGACGGTGCCACCATGAAGACCTTTTGCGGCACACCTGAGTACCTGGCCCCCGAGGTGCTGGAGGACAATGACTACGGCCGTGCAGTGGACTGGTGGGGGCTGGGCGTGGTCATGTACGAGATGATGTGCGGTCGCCTGCCCTTCTACAACCAGGACCATGAGAAGCTTTTTGAGCTCATCCTCATGGAGGAGATCCGCTTCCCGCGCACGCTTGGTCCCGAGGCCAAGTCCTTGCTTTCAGGGCTGCTCAAGAAGGACCCCAAGCAGAGGCTTGGCGGGGGCTCCGAGGACGCCAAGGAGATCATGCAGCATCGCTTCTTTGCCGGTATCGTGTGGCAGCACGTGTACGAGAAGAAGCTCAGCCCACCCTTCAAGCCCCAGGTCACGTCGGAGACTGACACCAGGTATTTTGATGAGGAGTTCACGGCCCAGATGATCACCATCACACCACCTGACCAAGATGACAGCATGGAGTGTGTGGACAGCGAGCGCAGGCCCCACTTCCCCCAGTTCTCCTACTCGGCCAGCGGCACGGCC> SEQ ID NO: 16> TBL1XR1 WT-79-4927-7786-8905.2Atty. Dkt. No.: 121384-0285> Length: 1545ATGAGTATAAGCAGTGATGAGGTCAACTTCTTGGTATATAGATACTTGCAAGAGTCAGGATTTTCTCATTCAGCATTTACCTTTGGTATAGAAAGCCATATCAGTCAGTCCAATATAAATGGTGCCCTCGTCCCACCCGCTGCATTGATTTCTATCATCCAGAAAGGTCTACAGTATGTAGAAGCAGAAGTTAGTATTAATGAGGATGGTACCTTGTTTGATGGTCGACCAATAGAGTCTCTGTCCCTGATAGATGCCGTAATGCCTGATGTAGTACAAACAAGACAACAAGCTTATAGAGATAAGCTTGCACAGCAACAGGCAGCAGCTGCTGCAGCTGCCGCAGCTGCAGCCAGCCAACAAGGATCTGCAAAAAATGGAGAAAACACAGCAAATGGGGAGGAGAATGGAGCACATACTATAGCAAATAATCATACTGATATGATGGAAGTGGATGGGGATGTTGAAATCCCTCCTAATAAAGCTGTTGTGTTGCGGGGCCATGAATCTGAAGTTTTTATCTGTGCCTGGAACCCTGTTAGTGATCTCCTAGCATCAGGGTCTGGAGACTCAACAGCAAGAATATGGAATCTTAGTGAGAACAGCACCAGTGGCTCTACACAGTTAGTACTTAGACATTGTATACGAGAAGGAGGGCAAGATGTTCCAAGCAACAAGGATGTCACATCTCTAGATTGGAATAGTGAAGGTACACTTCTAGCAACTGGTTCCTATGATGGGTTTGCCAGAATATGGACTAAAGATGGTAACCTTGCTAGCACCTTAGGGCAGCATAAAGGCCCTATATTTGCATTAAAATGGAATAAGAAAGGAAATTTCATCCTAAGTGCTGGAGTAGACAAGACTACAATTATTTGGGACGCACATACTGGTGAAGCCAAGCAACAGTTTCCTTTTCATTCAGCACCAGCATTGGATGTTGATTGGCAGAGCAACAACACCTTTGCTTCTTGTAGTACAGATATGTGCATTCATGTCTGTAAATTAGGACAAGACAGACCTATTAAAACATTCCAAGGACATACGAATGAAGTAAATGCTATCAAATGGGACCCAACTGGCAATCTCTTGGCCTCCTGTTCTGACGACATGACTTTAAAGATATGGAGTATGAAACAAGACAATTGTGTCCATGATTTGCAAGCACATAATAAAGAAATTTATACTATCAAATGGAGTCCAACAGGACCAGGGACTAATAATCCAAATGCCAACCTTATGTTAGCAAGTGCATCCTTTGATTCTACTGTTAGGTTATGGGATGTAGACCGAGGGATATGCATCCATACCTTGACAAAACACCAAGAGCCTGTGTACAGTGTAGCTTTCAGTCCTGATGGCAGGTATCTGGCAAGTGGTTCTTTTGACAAATGTGTACACATCTGGAACACGCAGACAGGTGCTCTAGTTCACAGCTATAGGGGAACAGGTGGAATATTTGAAGTTTGCTGGAATGCAGCAGGAGACAAAGTTGGAGCCAGTGCATCAGATGGTTCAGTTTGTGTATTAGACCTTCGGAAATAG> SEQ ID NO: 17> IDH I WT> Length: 1242ATGTCCAAAAAAATCAGTGGCGGTTCTGTGGTAGAGATGCAAGGAGATGAAATGACACGAATCATTTGGGAATTGATTAAAGAGAAACTCATTTTTCCCTACGTGGAATTGGATCTACATAGCTATGATTTAGGCATAGAGAATCGTGATGCCACCAACGACCAAGTCACCAAGGATGCTGCAGAAGCTATAAAGAAGCATAATGTTGGCGTCAAATGTGCCACTATCACTCCTGATGAGAAGAGGGTTGAGGAGTTCAAGTTGAAACAAATGTGGAAATCACCAAATGGCACCATACGAAATATTCTGGGTGGCACGGTCTTCAGAGAAGCCATTATCTGCAAAAATATCCCCCGGCTTGTGAGTGGATGGGTAAAACCTATCATCATAGGTCGTCATGCTTATGGGGATCAATACAGAGCAACTGATTTTGTTGTTCCTGGGCCTGGAAAAGTAGAGATAACCTACACACCAAGTGACGGAACCCAAAAGGTGACAT-80-4927-7786-8905.2Atty. Dkt. No.: 121384-0285ACCTGGTACATAACTTTGAAGAAGGTGGTGGTGTTGCCATGGGGATGTATAATCAAGATAAGTCAATTGAAGATTTTGCACACAGTTCCTTCCAAATGGCTCTGTCTAAGGGTTGGCCTTTGTATCTGAGCACCAAAAACACTATTCTGAAGAAATATGATGGGCGTTTTAAAGACATCTTTCAGGAGATATATGACAAGCAGTACAAGTCCCAGTTTGAAGCTCAAAAGATCTGGTATGAGCATAGGCTCATCGACGACATGGTGGCCCAAGCTATGAAATCAGAGGGAGGCTTCATCTGGGCCTGTAAAAACTATGATGGTGACGTGCAGTCGGACTCTGTGGCCCAAGGGTATGGCTCTCTCGGCATGATGACCAGCGTGCTGGTTTGTCCAGATGGCAAGACAGTAGAAGCAGAGGCTGCCCACGGGACTGTAACCCGTCACTACCGCATGTACCAGAAAGGACAGGAGACGTCCACCAATCCCATTGCTTCCATTTTTGCCTGGACCAGAGGGTTAGCCCACAGAGCAAAGCTTGATAACAATAAAGAGCTTGCCTTCTTTGCAAATGCTTTGGAAGAAGTCTCTATTGAGACAATTGAGGCTGGCTTCATGACCAAGGACTTGGCTGCTTGCATTAAAGGTTTACCCAATGTGCAACGTTCTGACTACTTGAATACATTTGAGTTCATGGATAAACTTGGAGAAAACTTGAAGATCAAACTAGCTCAGGCCAAACTT> SEQ ID NO: 18>JAK3 A572T> Length: 3372ATGGCACCTCCAAGTGAAGAGACGCCCCTGATCCCTCAGCGTTCATGCAGCCTCTTGTCCACGGAGGCTGGTGCCCTGCATGTGCTGCTGCCCGCTCGGGGCCCCGGGCCCCCCCAGCGCCTATCTTTCTCCTTTGGGGACCACTTGGCTGAGGACCTGTGCGTGCAGGCTGCCAAGGCCAGCGGCATCCTGCCTGTGTACCACTCCCTCTTTGCTCTGGCCACGGAGGACCTGTCCTGCTGGTTCCCCCCGAGCCACATCTTCTCCGTGGAGGATGCCAGCACCCAAGTCCTGCTGTACAGGATTCGCTTTTACTTCCCCAATTGGTTTGGGCTGGAGAAGTGCCACCGCTTCGGGCTACGCAAGGATTTGGCCAGTGCTATCCTTGACCTGCCAGTCCTGGAGCACCTCTTTGCCCAGCACCGCAGTGACCTGGTGAGTGGGCGCCTCCCCGTGGGCCTCAGTCTCAAGGAGCAGGGTGAGTGTCTCAGCCTGGCCGTGTTGGACCTGGCCCGGATGGCGCGAGAGCAGGCCCAGCGGCCGGGAGAGCTGCTGAAGACTGTCAGCTACAAGGCCTGCCTACCCCCAAGCCTGCGCGACCTGATCCAGGGCCTGAGCTTCGTGACGCGGAGGCGTATTCGGAGGACGGTGCGCAGAGCCCTGCGCCGCGTGGCCGCCTGCCAGGCAGACCGGCACTCGCTCATGGCCAAGTACATCATGGACCTGGAGCGGCTGGATCCAGCCGGGGCCGCCGAGACCTTCCACGTGGGCCTCCCTGGGGCCCTTGGTGGCCACGACGGGCTGGGGCTGCTCCGCGTGGCTGGTGACGGCGGCATCGCCTGGACCCAGGGAGAACAGGAGGTCCTCCAGCCCTTCTGCGACTTTCCAGAAATCGTAGACATTAGCATCAAGCAGGCCCCGCGCGTTGGCCCGGCCGGAGAGCACCGCCTGGTCACTGTTACCAGGACAGACAACCAGATTTTAGAGGCCGAGTTCCCAGGGCTGCCCGAGGCTCTGTCGTTCGTGGCGCTCGTGGACGGCTACTTCCGGCTGACCACGGACTCCCAGCACTTCTTCTGCAAGGAGGTGGCACCGCCGAGGCTGCTGGAGGAAGTGGCCGAGCAGTGCCACGGCCCCATCACTCTGGACTTTGCCATCAACAAGCTCAAGACTGGGGGCTCACGTCCTGGCTCCTATGTTCTCCGCCGCAGCCCCCAGGACTTTGACAGCTTCCTCCTCACTGTCTGTGTCCAGAACCCCCTTGGTCCTGATTATAAGGGCTGCCTCATCCGGCGCAGCCCCACAGGAACCTTCCTTCTGGTTGGCCTCAGCCGACCCCACAGCAGTCTTCGAGAGCTCCTGGCAACCTGCTGGG-81-4927-7786-8905.2Atty. Dkt. No.: 121384-0285ATGGGGGGCTGCACGTAGATGGGGTGGCAGTGACCCTCACTTCCTGCTGTATCCCCAGACCCAAAGAAAAGTCCAACCTGATCGTGGTCCAGAGAGGTCACAGCCCACCCACATCATCCTTGGTTCAGCCCCAATCCCAATACCAGCTGAGTCAGATGACATTTCACAAGATCCCTGCTGACAGCCTGGAGTGGCATGAGAACCTGGGCCATGGGTCCTTCACCAAGATTTACCGGGGCTGTCGCCATGAGGTGGTGGATGGGGAGGCCCGAAAGACAGAGGTGCTGCTGAAGGTCATGGATGCCAAGCACAAGAACTGCATGGAGTCATTCCTGGAAACAGCGAGCTTGATGAGCCAAGTGTCGTACCGGCATCTCGTGCTGCTCCACGGCGTGTGCATGGCTGGAGACAGCACCATGGTGCAGGAATTTGTACACCTGGGGGCCATAGACATGTATCTGCGAAAACGTGGCCACCTGGTGCCAGCCAGCTGGAAGCTGCAGGTGGTCAAACAGCTGGCCTACGCCCTCAACTATCTGGAGGACAAAGGCCTGCCCCATGGCAATGTCTCTGCCCGGAAGGTGCTCCTGGCTCGGGAGGGGGCTGATGGGAGCCCGCCCTTCATCAAGCTGAGTGACCCTGGGGTCAGCCCCGCTGTGTTAAGCCTGGAGATGCTCACCGACAGGATCCCCTGGGTGGCCCCCGAGTGTCTCCGGGAGGCGCAGACACTTAGCTTGGAAGCTGACAAGTGGGGCTTCGGCGCCACGGTCTGGGAAGTGTTTAGTGGCGTCACCATGCCCATCAGTGCCCTGGATCCTGCTAAGAAACTCCAATTTTATGAGGACCGGCAGCAGCTGCCGGCCCCCAAGTGGACAGAGCTGGCCCTGCTGATTCAACAGTGCATGGCCTATGAGCCGGTCCAGAGGCCCTCCTTCCGAGCCGTCATTCGTGACCTCAATAGCCTCATCTCTTCAGACTATGAGCTCCTCTCAGACCCCACACCTGGTGCCCTGGCACCTCGTGATGGGCTGTGGAATGGTGCCCAGCTCTATGCCTGCCAAGACCCCACGATCTTCGAGGAGAGACACCTCAAGTACATCTCACAGCTGGGCAAGGGCAACTTTGGCAGCGTGGAGCTGTGCCGCTATGACCCGCTAGGCGACAATACAGGTGCCCTGGTGGCCGTGAAACAGCTGCAGCACAGCGGGCCAGACCAGCAGAGGGACTTTCAGCGGGAGATTCAGATCCTCAAAGCACTGCACAGTGATTTCATTGTCAAGTATCGTGGTGTCAGCTATGGCCCGGGCCGCCAGAGCCTGCGGCTGGTCATGGAGTACCTGCCCAGCGGCTGCTTGCGCGACTTCCTGCAGCGGCACCGCGCGCGCCTCGATGCCAGCCGCCTCCTTCTCTATTCCTCGCAGATCTGCAAGGGCATGGAGTACCTGGGCTCCCGCCGCTGCGTGCACCGCGACCTGGCCGCCCGAAACATCCTCGTGGAGAGCGAGGCACACGTCAAGATCGCTGACTTCGGCCTAGCTAAGCTGCTGCCGCTTGACAAAGACTACTACGTGGTCCGCGAGCCAGGCCAGAGCCCCATTTTCTGGTATGCCCCCGAATCCCTCTCGGACAACATCTTCTCTCGCCAGTCAGACGTCTGGAGCTTCGGGGTCGTCCTGTACGAGCTCTTCACCTACTGCGACAAAAGCTGCAGCCCCTCGGCCGAGTTCCTGCGGATGATGGGATGTGAGCGGGATGTCCCCGCCCTCTGCCGCCTCTTGGAACTGCTGGAGGAGGGCCAGAGGCTGCCGGCGCCTCCTGCCTGCCCTGCTGAGGTTCACGAGCTCATGAAGCTGTGCTGGGCCCCTAGCCCACAGGACCGGCCATCATTCAGCGCCCTGGGCCCCCAGCTGGACATGCTGTGGAGCGGAAGCCGGGGGTGTGAGACTCATGCCTTCACTGCTCACCCAGAGGGCAAACACCACTCCCTGTCCTTTTCA> SEQ ID NO: 19> JAK3 G589D> Length: 3375 nucleotidesATGGCACCTCCAAGTGAAGAGACGCCCCTGATCCCTCAGCGTTCATGCAGCCTCTTGTCCACGGAGGCTGGTGCCCTGCATGTGCTGCTGCCCGCTCGGGGCCCCGGGCC-82-4927-7786-8905.2Atty. Dkt. No.: 121384-0285CCCCCAGCGCCTATCTTTCTCCTTTGGGGACCACTTGGCTGAGGACCTGTGCGTGCAGGCTGCCAAGGCCAGCGGCATCCTGCCTGTGTACCACTCCCTCTTTGCTCTGGCCACGGAGGACCTGTCCTGCTGGTTCCCCCCGAGCCACATCTTCTCCGTGGAGGATGCCAGCACCCAAGTCCTGCTGTACAGGATTCGCTTTTACTTCCCCAATTGGTTTGGGCTGGAGAAGTGCCACCGCTTCGGGCTACGCAAGGATTTGGCCAGTGCTATCCTTGACCTGCCAGTCCTGGAGCACCTCTTTGCCCAGCACCGCAGTGACCTGGTGAGTGGGCGCCTCCCCGTGGGCCTCAGTCTCAAGGAGCAGGGTGAGTGTCTCAGCCTGGCCGTGTTGGACCTGGCCCGGATGGCGCGAGAGCAGGCCCAGCGGCCGGGAGAGCTGCTGAAGACTGTCAGCTACAAGGCCTGCCTACCCCCAAGCCTGCGCGACCTGATCCAGGGCCTGAGCTTCGTGACGCGGAGGCGTATTCGGAGGACGGTGCGCAGAGCCCTGCGCCGCGTGGCCGCCTGCCAGGCAGACCGGCACTCGCTCATGGCCAAGTACATCATGGACCTGGAGCGGCTGGATCCAGCCGGGGCCGCCGAGACCTTCCACGTGGGCCTCCCTGGGGCCCTTGGTGGCCACGACGGGCTGGGGCTGCTCCGCGTGGCTGGTGACGGCGGCATCGCCTGGACCCAGGGAGAACAGGAGGTCCTCCAGCCCTTCTGCGACTTTCCAGAAATCGTAGACATTAGCATCAAGCAGGCCCCGCGCGTTGGCCCGGCCGGAGAGCACCGCCTGGTCACTGTTACCAGGACAGACAACCAGATTTTAGAGGCCGAGTTCCCAGGGCTGCCCGAGGCTCTGTCGTTCGTGGCGCTCGTGGACGGCTACTTCCGGCTGACCACGGACTCCCAGCACTTCTTCTGCAAGGAGGTGGCACCGCCGAGGCTGCTGGAGGAAGTGGCCGAGCAGTGCCACGGCCCCATCACTCTGGACTTTGCCATCAACAAGCTCAAGACTGGGGGCTCACGTCCTGGCTCCTATGTTCTCCGCCGCAGCCCCCAGGACTTTGACAGCTTCCTCCTCACTGTCTGTGTCCAGAACCCCCTTGGTCCTGATTATAAGGGCTGCCTCATCCGGCGCAGCCCCACAGGAACCTTCCTTCTGGTTGGCCTCAGCCGACCCCACAGCAGTCTTCGAGAGCTCCTGGCAACCTGCTGGGATGGGGGGCTGCACGTAGATGGGGTGGCAGTGACCCTCACTTCCTGCTGTATCCCCAGACCCAAAGAAAAGTCCAACCTGATCGTGGTCCAGAGAGGTCACAGCCCACCCACATCATCCTTGGTTCAGCCCCAATCCCAATACCAGCTGAGTCAGATGACATTTCACAAGATCCCTGCTGACAGCCTGGAGTGGCATGAGAACCTGGGCCATGGGTCCTTCACCAAGATTTACCGGGGCTGTCGCCATGAGGTGGTGGATGGGGAGGCCCGAAAGACAGAGGTGCTGCTGAAGGTCATGGATGCCAAGCACAAGAACTGCATGGAGTCATTCCTGGAAGCAGCGAGCTTGATGAGCCAAGTGTCGTACCGGCATCTCGTGCTGCTCCACGACGTGTGCATGGCTGGAGACAGCACCATGGTGCAGGAATTTGTACACCTGGGGGCCATAGACATGTATCTGCGAAAACGTGGCCACCTGGTGCCAGCCAGCTGGAAGCTGCAGGTGGTCAAACAGCTGGCCTACGCCCTCAACTATCTGGAGGACAAAGGCCTGCCCCATGGCAATGTCTCTGCCCGGAAGGTGCTCCTGGCTCGGGAGGGGGCTGATGGGAGCCCGCCCTTCATCAAGCTGAGTGACCCTGGGGTCAGCCCCGCTGTGTTAAGCCTGGAGATGCTCACCGACAGGATCCCCTGGGTGGCCCCCGAGTGTCTCCGGGAGGCGCAGACACTTAGCTTGGAAGCTGACAAGTGGGGCTTCGGCGCCACGGTCTGGGAAGTGTTTAGTGGCGTCACCATGCCCATCAGTGCCCTGGATCCTGCTAAGAAACTCCAATTTTATGAGGACCGGCAGCAGCTGCCGGCCCCCAAGTGGACAGAGCTGGCCCTGCTGATTCAACAGTGCATGGCCTATGAGCCGGTCCAGAGGCCCTCCTTCCGAGCCGTCATTCGTGACCTCAATAGCCTCATCTCTTCAGACTATGAGCTCCTCTCAGACCCCACACCTGGTGCCCTGGCACCTCGTGATGGGCTGTGGAATGGTGCCCAGCTCTATGCCTGCCAAGACCCCACGATCTTCGAGGAGAGACACCTCAAGTACATCTCACAGCTGGGCAAGGGCAACTTTGGCAGCGTGGAGCTGTGCCGCTATGACCCGCTAGGCGACAATACAGGTGCCCTGGTGGCCGTGAAACAGCTGCAGCACAGCGGGCCAGACCAGCAGAGGGACTTTCAGCGGGAGATTCAGATCCTCAAAGCACTGCACAGTGATTTCATTGTCAAGTATCGTGGTGTCAGCTATGGCCCGGGCCGCCAGAGCCTGCG-83-4927-7786-8905.2Atty. Dkt. No.: 121384-0285GCTGGTCATGGAGTACCTGCCCAGCGGCTGCTTGCGCGACTTCCTGCAGCGGCACCGCGCGCGCCTCGATGCCAGCCGCCTCCTTCTCTATTCCTCGCAGATCTGCAAGGGCATGGAGTACCTGGGCTCCCGCCGCTGCGTGCACCGCGACCTGGCCGCCCGAAACATCCTCGTGGAGAGCGAGGCACACGTCAAGATCGCTGACTTCGGCCTAGCTAAGCTGCTGCCGCTTGACAAAGACTACTACGTGGTCCGCGAGCCAGGCCAGAGCCCCATTTTCTGGTATGCCCCCGAATCCCTCTCGGACAACATCTTCTCTCGCCAGTCAGACGTCTGGAGCTTCGGGGTCGTCCTGTACGAGCTCTTCACCTACTGCGACAAAAGCTGCAGCCCCTCGGCCGAGTTCCTGCGGATGATGGGATGTGAGCGGGATGTCCCCGCCCTCTGCCGCCTCTTGGAACTGCTGGAGGAGGGCCAGAGGCTGCCGGCGCCTCCTGCCTGCCCTGCTGAGGTTCACGAGCTCATGAAGCTGTGCTGGGCCCCTAGCCCACAGGACCGGCCATCATTCAGCGCCCTGGGCCCCCAGCTGGACATGCTGTGGAGCGGAAGCCGGGGGTGTGAGACTCATGCCTTCACTGCTCACCCAGAGGGCAAACACCACTCCCTGTCCTTTTCATAG> SEQ ID NO: 20> JAK3 H583Y> Length: 3375 nucleotidesATGGCACCTCCAAGTGAAGAGACGCCCCTGATCCCTCAGCGTTCATGCAGCCTCTTGTCCACGGAGGCTGGTGCCCTGCATGTGCTGCTGCCCGCTCGGGGCCCCGGGCCCCCCCAGCGCCTATCTTTCTCCTTTGGGGACCACTTGGCTGAGGACCTGTGCGTGCAGGCTGCCAAGGCCAGCGGCATCCTGCCTGTGTACCACTCCCTCTTTGCTCTGGCCACGGAGGACCTGTCCTGCTGGTTCCCCCCGAGCCACATCTTCTCCGTGGAGGATGCCAGCACCCAAGTCCTGCTGTACAGGATTCGCTTTTACTTCCCCAATTGGTTTGGGCTGGAGAAGTGCCACCGCTTCGGGCTACGCAAGGATTTGGCCAGTGCTATCCTTGACCTGCCAGTCCTGGAGCACCTCTTTGCCCAGCACCGCAGTGACCTGGTGAGTGGGCGCCTCCCCGTGGGCCTCAGTCTCAAGGAGCAGGGTGAGTGTCTCAGCCTGGCCGTGTTGGACCTGGCCCGGATGGCGCGAGAGCAGGCCCAGCGGCCGGGAGAGCTGCTGAAGACTGTCAGCTACAAGGCCTGCCTACCCCCAAGCCTGCGCGACCTGATCCAGGGCCTGAGCTTCGTGACGCGGAGGCGTATTCGGAGGACGGTGCGCAGAGCCCTGCGCCGCGTGGCCGCCTGCCAGGCAGACCGGCACTCGCTCATGGCCAAGTACATCATGGACCTGGAGCGGCTGGATCCAGCCGGGGCCGCCGAGACCTTCCACGTGGGCCTCCCTGGGGCCCTTGGTGGCCACGACGGGCTGGGGCTGCTCCGCGTGGCTGGTGACGGCGGCATCGCCTGGACCCAGGGAGAACAGGAGGTCCTCCAGCCCTTCTGCGACTTTCCAGAAATCGTAGACATTAGCATCAAGCAGGCCCCGCGCGTTGGCCCGGCCGGAGAGCACCGCCTGGTCACTGTTACCAGGACAGACAACCAGATTTTAGAGGCCGAGTTCCCAGGGCTGCCCGAGGCTCTGTCGTTCGTGGCGCTCGTGGACGGCTACTTCCGGCTGACCACGGACTCCCAGCACTTCTTCTGCAAGGAGGTGGCACCGCCGAGGCTGCTGGAGGAAGTGGCCGAGCAGTGCCACGGCCCCATCACTCTGGACTTTGCCATCAACAAGCTCAAGACTGGGGGCTCACGTCCTGGCTCCTATGTTCTCCGCCGCAGCCCCCAGGACTTTGACAGCTTCCTCCTCACTGTCTGTGTCCAGAACCCCCTTGGTCCTGATTATAAGGGCTGCCTCATCCGGCGCAGCCCCACAGGAACCTTCCTTCTGGTTGGCCTCAGCCGACCCCACAGCAGTCTTCGAGAGCTCCTGGCAACCTGCTGGG ATGGGGGGCTGCACGTAGATGGGGTGGCAGTGACCCTCACTTCCTGCTGTATCCCC-84-4927-7786-8905.2Atty. Dkt. No.: 121384-0285AGACCCAAAGAAAAGTCCAACCTGATCGTGGTCCAGAGAGGTCACAGCCCACCCACATCATCCTTGGTTCAGCCCCAATCCCAATACCAGCTGAGTCAGATGACATTTCACAAGATCCCTGCTGACAGCCTGGAGTGGCATGAGAACCTGGGCCATGGGTCCTTCACCAAGATTTACCGGGGCTGTCGCCATGAGGTGGTGGATGGGGAGGCCCGAAAGACAGAGGTGCTGCTGAAGGTCATGGATGCCAAGCACAAGAACTGCATGGAGTCATTCCTGGAAGCAGCGAGCTTGATGAGCCAAGTGTCGTACCGGTATCTCGTGCTGCTCCACGGCGTGTGCATGGCTGGAGACAGCACCATGGTGCAGGAATTTGTACACCTGGGGGCCATAGACATGTATCTGCGAAAACGTGGCCACCTGGTGCCAGCCAGCTGGAAGCTGCAGGTGGTCAAACAGCTGGCCTACGCCCTCAACTATCTGGAGGACAAAGGCCTGCCCCATGGCAATGTCTCTGCCCGGAAGGTGCTCCTGGCTCGGGAGGGGGCTGATGGGAGCCCGCCCTTCATCAAGCTGAGTGACCCTGGGGTCAGCCCCGCTGTGTTAAGCCTGGAGATGCTCACCGACAGGATCCCCTGGGTGGCCCCCGAGTGTCTCCGGGAGGCGCAGACACTTAGCTTGGAAGCTGACAAGTGGGGCTTCGGCGCCACGGTCTGGGAAGTGTTTAGTGGCGTCACCATGCCCATCAGTGCCCTGGATCCTGCTAAGAAACTCCAATTTTATGAGGACCGGCAGCAGCTGCCGGCCCCCAAGTGGACAGAGCTGGCCCTGCTGATTCAACAGTGCATGGCCTATGAGCCGGTCCAGAGGCCCTCCTTCCGAGCCGTCATTCGTGACCTCAATAGCCTCATCTCTTCAGACTATGAGCTCCTCTCAGACCCCACACCTGGTGCCCTGGCACCTCGTGATGGGCTGTGGAATGGTGCCCAGCTCTATGCCTGCCAAGACCCCACGATCTTCGAGGAGAGACACCTCAAGTACATCTCACAGCTGGGCAAGGGCAACTTTGGCAGCGTGGAGCTGTGCCGCTATGACCCGCTAGGCGACAATACAGGTGCCCTGGTGGCCGTGAAACAGCTGCAGCACAGCGGGCCAGACCAGCAGAGGGACTTTCAGCGGGAGATTCAGATCCTCAAAGCACTGCACAGTGATTTCATTGTCAAGTATCGTGGTGTCAGCTATGGCCCGGGCCGCCAGAGCCTGCGGCTGGTCATGGAGTACCTGCCCAGCGGCTGCTTGCGCGACTTCCTGCAGCGGCACCGCGCGCGCCTCGATGCCAGCCGCCTCCTTCTCTATTCCTCGCAGATCTGCAAGGGCATGGAGTACCTGGGCTCCCGCCGCTGCGTGCACCGCGACCTGGCCGCCCGAAACATCCTCGTGGAGAGCGAGGCACACGTCAAGATCGCTGACTTCGGCCTAGCTAAGCTGCTGCCGCTTGACAAAGACTACTACGTGGTCCGCGAGCCAGGCCAGAGCCCCATTTTCTGGTATGCCCCCGAATCCCTCTCGGACAACATCTTCTCTCGCCAGTCAGACGTCTGGAGCTTCGGGGTCGTCCTGTACGAGCTCTTCACCTACTGCGACAAAAGCTGCAGCCCCTCGGCCGAGTTCCTGCGGATGATGGGATGTGAGCGGGATGTCCCCGCCCTCTGCCGCCTCTTGGAACTGCTGGAGGAGGGCCAGAGGCTGCCGGCGCCTCCTGCCTGCCCTGCTGAGGTTCACGAGCTCATGAAGCTGTGCTGGGCCCCTAGCCCACAGGACCGGCCATCATTCAGCGCCCTGGGCCCCCAGCTGGACATGCTGTGGAGCGGAAGCCGGGGGTGTGAGACTCATGCCTTCACTGCTCACCCAGAGGGCAAACACCACTCCCTGTCCTTTTCATAG> SEQ ID NO: 21> RPL10 R98S> Length: 642 nucleotidesATGGGCCGCCGCCCCGCCCGTTGTTACCGGTATTGTAAGAACAAGCCGTACCCAAAGTCTCGCTTCTGCCGAGGTGTCCCTGATGCCAAGATTCGCATTTTTGACCTGGGGCGGAAAAAGGCAAAAGTGGATGAGTTTCCGCTTTGTGGCCACATGGTGTCAGATG-85-4927-7786-8905.2Atty. Dkt. No.: 121384-0285AATATGAGCAGCTGTCCTCTGAAGCCCTGGAGGCTGCCCGAATTTGTGCCAATAAGTACATGGTAAAAAGTTGTGGCAAAGATGGCTTCCATATCCGGGTGCGGCTCCACCCCTTCCACGTCATCAGCATCAACAAGATGTTGTCCTGTGCTGGGGCTGACAGGCTCCAAACAGGCATGCGAGGTGCCTTTGGAAAGCCCCAGGGCACTGTGGCCAGGGTTCACATTGGCCAAGTTATCATGTCCATCCGCACCAAGCTGCAGAACAAGGAGCATGTGATTGAGGCCCTGCGCAGGGCCAAGTTCAAGTTTCCTGGCCGCCAGAAGATCCACATCTCAAAGAAGTGGGGCTTCACCAAGTTCAATGCTGATGAATTTGAAGACATGGTGGCTGAAAAGCGGCTCATCCCAGATGGCTGTGGGGTCAAGTACATCCCCAGTCGTGGCCCTCTGGACAAGTGGCGGGCCCTGCACTCASEQ ID NO: 22> TLDC1 S87F> Length: 1368 nucleotidesATGGGGAACAGCAGAAGCCGTGTGGGGCGGAGCTTTTGTTCACAGTTTCTTCCTGAGGAACAGGCAGAGATTGATCAATTGTTTGATGCTCTGTCATCAGATAAAAACAGCCCGAATGTCTCATCCAAATCCTTCTCTCTGAAGGCACTACAGAACCACGTCGGGGAAGCTCTTCCCCCAGAGATGGTCACCAGGCTGTATGATGGCATGCGGAGGGTCGACCTGACAGGGAAGGCGAAGGGACCCAGTGAGAACGTGTTCCAGGAGCAGTTCACAGCATCCATGTCCCACCTGTTGAAAGGAAACTCCGAGGAGAAGAGTCTCATGATTATGAAAATGATTTCTGCCACAGAAGGTCCCGTGAAGGCCAGAGAAGTCCAAAAGTTTACAGAGGATCTGGTTGGCTCTGTGGTGCACGTGCTAAGCCACAGACAGGAGCTGAGAGGCTGGACTGGGAAGGAAGCCCCAGGGCCCAACCCCCGGGTGCAGGTGCTGGCTGCTCAGCTGCTCTCTGACATGAAGCTGCAAGATGGCAAGAGACTTCTGGGGCCCCAGTGGCTGGACTATGACTGTGACCGAGCTGTGATCGAGGACTGGGTGTTCAGGGTCCCCCATGTGGCCATATTCCTGAGTGTGGTCATTTGCAAGGGCTTTCTCATCCTGTGCTCGTCTCTTGATCTGACTACCCTGGTCCCTGAGCGTCAAGTGGACCAGGGCAGGGGTTTTGAGAGCATCCTGGATGTCCTCTCTGTCATGTACATCAACGCCCAGCTGCCTCGGGAGCAGCGGCACCGCTGGTGCCTGCTCTTTTCGTCTGAGCTCCATGGACACAGCTTCTCCCAGCTCTGTGGCCACATCACTCACCGGGGACCCTGTGTGGCTGTCCTCGAGGACCATGACAAGCATGTGTTCGGTGGGTTTGCCTCTTGCTCTTGGGAGGTGAAGCCTCAGTTTCAAGGGGACAACAGATGCTTCCTGTTCTCCATCTGCCCCAGCATGGCTGTGTACACACACACGGGCTACAACGACCACTACATGTACTTGAACCATGGACAGCAGACGATCCCGAACGGACTGGGTATGGGGGGGCAGCACAATTACTTTGGGCTTTGGGTGGATGTTGATTTTGGGAAAGGACACAGCAGAGCCAAGCCCACGTGCACCACGTACAACAGCCCGCAGCTGTCGGCTCAGGAGAACTTCCAGTTTGATAAGATGGAGGTGTGGGCGGTTGGAGACCCCTCAGAGGAGCAGTTGGCCAAGGGCAACAAGAGCATCCTGGATGCGGACCCTGAGGCCCAGGCCCTGCTGGAGATCAGTGGGCATTCGCGCCACAGCGAAGGGCTCCGGGAAGTCCCGGACGATGAA> SEQ ID NO: 234927-7786-8905.2Atty. Dkt. No.: 121384-0285> STAT3 G618R> Length: 2310 nucleotidesATGGCCCAATGGAATCAGCTACAGCAGCTTGACACACGGTACCTGGAGCAGCTCC ATCAGCTCTACAGTGACAGCTTCCCAATGGAGCTGCGGCAGTTTCTGGCCCCTTG GATTGAGAGTCAAGATTGGGCATATGCGGCCAGCAAAGAATCACATGCCACTTTG GTGTTTCATAATCTCCTGGGAGAGATTGACCAGCAGTATAGCCGCTTCCTGCAAGA GTCGAATGTTCTCTATCAGCACAATCTACGAAGAATCAAGCAGTTTCTTCAGAGCA GGTATCTTGAGAAGCCAATGGAGATTGCCCGGATTGTGGCCCGGTGCCTGTGGGA AGAATCACGCCTTCTACAGACTGCAGCCACTGCGGCCCAGCAAGGGGGCCAGGC CAACCACCCCACAGCAGCCGTGGTGACGGAGAAGCAGCAGATGCTGGAGCAGCA CCTTCAGGATGTCCGGAAGAGAGTGCAGGATCTAGAACAGAAAATGAAAGTGGTAGAGAATCTCCAGGATGACTTTGATTTCAACTATAAAACCCTCAAGAGTCAAGGA GACATGCAAGATCTGAATGGAAACAACCAGTCAGTGACCAGGCAGAAGATGCAG CAGCTGGAACAGATGCTCACTGCGCTGGACCAGATGCGGAGAAGCATCGTGAGT GAGCTGGCGGGGCTTTTGTCAGCGATGGAGTACGTGCAGAAAACTCTCACGGAC GAGGAGCTGGCTGACTGGAAGAGGCGGCAACAGATTGCCTGCATTGGAGGCCCG CCCAACATCTGCCTAGATCGGCTAGAAAACTGGATAACGTCATTAGCAGAATCTCA ACTTCAGACCCGTCAACAAATTAAGAAACTGGAGGAGTTGCAGCAAAAAGTTTC CTACAAAGGGGACCCCATTGTACAGCACCGGCCGATGCTGGAGGAGAGAATCGTG GAGCTGTTTAGAAACTTAATGAAAAGTGCCTTTGTGGTGGAGCGGCAGCCCTGCATGCCCATGCATCCTGACCGGCCCCTCGTCATCAAGACCGGCGTCCAGTTCACTACT AAAGTCAGGTTGCTGGTCAAATTCCCTGAGTTGAATTATCAGCTTAAAATTAAAGT GTGCATTGACAAAGACTCTGGGGACGTTGCAGCTCTCAGAGGATCCCGGAAATTT AACATTCTGGGCACAAACACAAAAGTGATGAACATGGAAGAATCCAACAACGGC AGCCTCTCTGCAGAATTCAAACACTTGACCCTGAGGGAGCAGAGATGTGGGAATG GGGGCCGAGCCAATTGTGATGCTTCCCTGATTGTGACTGAGGAGCTGCACCTGAT CACCTTTGAGACCGAGGTGTATCACCAAGGCCTCAAGATTGACCTAGAGACCCAC TCCTTGCCAGTTGTGGTGATCTCCAACATCTGTCAGATGCCAAATGCCTGGGCGTC CATCCTGTGGTACAACATGCTGACCAACAATCCCAAGAATGTAAACTTTTTTACCAAGCCCCCAATTGGAACCTGGGATCAAGTGGCCGAGGTCCTGAGCTGGCAGTTCTC CTCCACCACCAAGCGAGGACTGAGCATCGAGCAGCTGACTACACTGGCAGAGAA ACTCTTGGGACCTGGTGTGAATTATTCAGGGTGTCAGATCACATGGGCTAAATTTT GCAAAGAAAACATGGCTGGCAAGGGCTTCTCCTTCTGGGTCTGGCTGGACAATAT CATTGACCTTGTGAAAAAGTACATCCTGGCCCTTTGGAACGAAGGGTACATCATGG GCTTTATCAGTAAGGAGCGGGAGCGGGCCATCTTGAGCACTAAGCCTCCAGGCAC CTTCCTGCTAAGATTCAGTGAAAGCAGCAAAGAAGGACGCGTCACTTTCACTTGG GTGGAGAAGGACATCAGCGGTAAGACCCAGATCCAGTCCGTGGAACCATACACA AAGCAGCAGCTGAACAACATGTCATTTGCTGAAATCATCATGGGCTATAAGATCATGGATGCTACCAATATCCTGGTGTCTCCACTGGTCTATCTCTATCCTGACATTCCCAA GGAGGAGGCATTCGGAAAGTATTGTCGGCCAGAGAGCCAGGAGCATCCTGAAGC TGACCCAGGTAGCGCTGCCCCATACCTGAAGACCAAGTTTATCTGTGTGACACCA ACGACCTGCAGCAATACCATTGACCTGCCGATGTCCCCCCGCACTTTAGATTCATT GATGCAGTTTGGAAATAATGGTGAAGGTGCTGAACCCTCAGCAGGAGGGCAGTTT GAGTCCCTCACCTTTGACATGGAGTTGACCTCGGAGTGCGCTACCTCCCCCATG-87-4927-7786-8905.2Atty. Dkt. No.: 121384-0285> SEQ ID NO: 24> DNMT3AR882H> Length: 2736 nucleotidesATGCCCGCCATGCCCTCCAGCGGCCCCGGGGACACCAGCAGCTCTGCTGCGGAGCGGGAGGAGGACCGAAAGGACGGAGAGGAGCAGGAGGAGCCGCGTGGCAAGGAGGAGCGCCAAGAGCCCAGCACCACGGCACGGAAGGTGGGGCGGCCTGGGAGGAAGCGCAAGCACCCCCCGGTGGAAAGCGGTGACACGCCAAAGGACCCTGCGGTGATCTCCAAGTCCCCATCCATGGCCCAGGACTCAGGCGCCTCAGAGCTATTACCCAATGGGGACTTGGAGAAGCGGAGTGAGCCCCAGCCAGAGGAGGGGAGCCCTGCTGGGGGGCAGAAGGGCGGGGCCCCAGCAGAGGGAGAGGGTGCAGCTGAGACCCTGCCTGAAGCCTCAAGAGCAGTGGAAAATGGCTGCTGCACCCCCAAGGAGGGCCGAGGAGCCCCTGCAGAAGCGGGCAAAGAACAGAAGGAGACCAACATCGAATCCATGAAAATGGAGGGCTCCCGGGGCCGGCTGCGGGGTGGCTTGGGCTGGGAGTCCAGCCTCCGTCAGCGGCCCATGCCGAGGCTCACCTTCCAGGCGGGGGACCCCTACTACATCAGCAAGCGCAAGCGGGACGAGTGGCTGGCACGCTGGAAAAGGGAGGCTGAGAAGAAAGCCAAGGTCATTGCAGGAATGAATGCTGTGGAAGAAAACCAGGGGCCCGGGGAGTCTCAGAAGGTGGAGGAGGCCAGCCCTCCTGCTGTGCAGCAGCCCACTGACCCCGCATCCCCCACTGTGGCTACCACGCCTGAGCCCGTGGGGTCCGATGCTGGGGACAAGAATGCCACCAAAGCAGGCGATGACGAGCCAGAGTACGAGGACGGCCGGGGCTTTGGCATTGGGGAGCTGGTGTGGGGGAAACTGCGGGGCTTCTCCTGGTGGCCAGGCCGCATTGTGTCTTGGTGGATGACGGGCCGGAGCCGAGCAGCTGAAGGCACCCGCTGGGTCATGTGGTTCGGAGACGGCAAATTCTCAGTGGTGTGTGTTGAGAAGCTGATGCCGCTGAGCTCGTTTTGCAGTGCGTTCCACCAGGCCACGTACAACAAGCAGCCCATGTACCGCAAAGCCATCTACGAGGTCCTGCAGGTGGCCAGCAGCCGCGCGGGGAAGCTGTTCCCGGTGTGCCACGACAGCGATGAGAGTGACACTGCCAAGGCCGTGGAGGTGCAGAACAAGCCCATGATTGAATGGGCCCTGGGGGGCTTCCAGCCTTCTGGCCCTAAGGGCCTGGAGCCACCAGAAGAAGAGAAGAATCCCTACAAAGAAGTGTACACGGACATGTGGGTGGAACCTGAGGCAGCTGCCTACGCACCACCTCCACCAGCCAAAAAGCCCCGGAAGAGCACAGCGGAGAAGCCCAAGGTCAAGGAGATTATTGATGAGCGCACAAGAGAGCGGCTGGTGTACGAGGTGCGGCAGAAGTGCCGGAACATTGAGGACATCTGCATCTCCTGTGGGAGCCTCAATGTTACCCTGGAACACCCCCTCTTCGTTGGAGGAATGTGCCAAAACTGCAAGAACTGCTTTCTGGAGTGTGCGTACCAGTACGACGACGACGGCTACCAGTCCTACTGCACCATCTGCTGTGGGGGCCGTGAGGTGCTCATGTGCGGAAACAACAACTGCTGCAGGTGCTTTTGCGTGGAGTGTGTGGACCTCTTGGTGGGGCCGGGGGCTGCCCAGGCAGCCATTAAGGAAGACCCCTGGAACTGCTACATGTGCGGGCACAAGGGTACCTACGGGCTGCTGCGGCGGCGAGAGGACTGGCCCTCCCGGCTCCAGATGTTCTTCGCTAATAACCACGACCAGGAATTTGACCCTCCAAAGGTTTACCCACCTGTCCCAGCTGAGAAGAGGAAGCCCATCCGGGTGCTGTCTCTCTTTGATGGAATCGCTACAGGGCTCCTGGTGCTGAAGGACTTGGGCATTCAGGTGGACCGCTACATTGCCTCGGAGGTGTGTGAGGACTCCATCACGGTGGGCATGGTGCGGCACCAGGGGAAGATCATGTACGTCGGGGACGTCCGCAGCGTCACACAGAAGCATATCCAGGAGTGGGGCCCATTCGATCTGGTGATTGGGGGC-88-4927-7786-8905.2Atty. Dkt. No.: 121384-0285AGTCCCTGCAATGACCTCTCCATCGTCAACCCTGCTCGCAAGGGCCTCTACGAGGGCACTGGCCGGCTCTTCTTTGAGTTCTACCGCCTCCTGCATGATGCGCGGCCCAAGGAGGGAGATGATCGCCCCTTCTTCTGGCTCTTTGAGAATGTGGTGGCCATGGGCGTTAGTGACAAGAGGGACATCTCGCGATTTCTCGAGTCCAACCCTGTGATGATTGATGCCAAAGAAGTGTCAGCTGCACACAGGGCCCGCTACTTCTGGGGTAACCTTCCCGGTATGAACAGGCCGTTGGCATCCACTGTGAATGATAAGCTGGAGCTGCAGGAGTGTCTGGAGCATGGCAGGATAGCCAAGTTCAGCAAAGTGAGGACCATTACTACGAGGTCAAACTCCATAAAGCAGGGCAAAGACCAGCATTTTCCTGTCTTCATGAATGAGAAAGAGGACATCTTATGGTGCACTGAAATGGAAAGGGTATTTGGTTTCCCAGTCCACTATACTGACGTCTCCAACATGAGCCACTTGGCGAGGCAGAGACTGCTGGGCCGGTCATGGAGCGTGCCAGTCATCCGCCACCTCTTCGCTCCGCTGAAGGAGTATTTTGCGT GTGTG> SEQ ID NO: 25> IL7R V78M> Length: 1380 nucleotidesATGACAATTCTAGGTACAACTTTTGGCATGGTTTTTTCTTTACTTCAAGTCGTTTCTGGAGAAAGTGGCTATGCTCAAAATGGAGACTTGGAAGATGCAGAACTGGATGACTACTCATTCTCATGCTATAGCCAGTTGGAAGTGAATGGATCGCAGCACTCACTGACCTGTGCTTTTGAGGACCCAGATGTCAACATCACCAATCTGGAATTTGAAATATGTGGGGCCCTCATGGAGGTAAAGTGCCTGAATTTCAGGAAACTACAAGAGATATATTTCATCGAGACAAAGAAATTCTTACTGATTGGAAAGAGCAATATATGTGTGAAGGTTGGAGAAAAGAGTCTAACCTGCAAAAAAATAGACCTAACCACTATAGTTAAACCTGAGGCTCCTTTTGACCTGAGTGTCGTCTATCGGGAAGGAGCCAATGACTTTGTGGTGACATTTAATACATCACACTTGCAAAAGAAGTATGTAAAAGTTTTAATGCACGATGTAGCTTACCGCCAGGAAAAGGATGAAAACAAATGGACGCATGTGAATTTATCCAGCACAAAGCTGACACTCCTGCAGAGAAAGCTCCAACCGGCAGCAATGTATGAGATTAAAGTTCGATCCATCCCTGATCACTATTTTAAAGGCTTCTGGAGTGAATGGAGTCCAAGTTATTACTTCAGAACTCCAGAGATCAATAATAGCTCAGGGGAGATGGATCCTATCTTACTAACCATCAGCATTTTGAGTTTTTTCTCTGTCGCTCTGTTGGTCATCTTGGCCTGTGTGTTATGGAAAAAAAGGATTAAGCCTATCGTATGGCCCAGTCTCCCCGATCATAAGAAGACTCTGGAACATCTTTGTAAGAAACCAAGAAAAAATTTAAATGTGAGTTTCAATCCTGAAAGTTTCCTGGACTGCCAGATTCATAGGGTGGATGACATTCAAGCTAGAGATGAAGTGGAAGGTTTTCTGCAAGATACGTTTCCTCAGCAACTAGAAGAATCTGAGAAGCAGAGGCTTGGAGGGGATGTGCAGAGCCCCAACTGCCCATCTGAGGATGTAGTCATCACTCCAGAAAGCTTTGGAAGAGATTCATCCCTCACATGCCTGGCTGGGAATGTCAGTGCATGTGACGCCCCTATTCTCTCCTCTTCCAGGTCCCTAGACTGCAGGGAGAGTGGCAAGAATGGGCCTCATGTGTACCAGGACCTCCTGCTTAGCCTTGGGACTACAAACAGCACGCTGCCCCCTCCATTTTCTCTCCAATCTGGAATCCTGACATTGAACCCAGTTGCTCAGGGTCAGCCCATTCTTACTTCCCTGGGATCAAATCAAGA AGAAGCATATGTCACCATGTCCAGCTTCTACCAAAACCAGTGA-89-4927-7786-8905.2Atty. Dkt. No.: 121384-0285> SEQ ID NO: 26> NFKB2 P882Q> Length: 2703 nucleotidesATGGAGAGTTGCTACAACCCAGGTCTGGATGGTATTATTGAATATGATGATTTCAAA TTGAACTCCTCCATTGTGGAACCCAAGGAGCCAGCCCCAGAAACAGCTGATGGCC CCTACCTGGTGATCGTGGAACAGCCTAAGCAGAGAGGCTTCCGATTTCGATATGGC TGTGAAGGCCCCTCCCATGGAGGACTGCCCGGTGCCTCCAGTGAGAAGGGCCGA AAGACCTATCCCACTGTCAAGATCTGTAACTACGAGGGACCAGCCAAGATCGAGG TGGACCTGGTAACACACAGTGACCCACCTCGTGCTCATGCCCACAGTCTGGTGGG CAAGCAATGCTCGGAGCTGGGGATCTGCGCCGTTTCTGTGGGGCCCAAGGACATG ACTGCCCAATTTAACAACCTGGGTGTCCTGCATGTGACTAAGAAGAACATGATGG GGACTATGATACAAAAACTTCAGAGGCAGCGGCTCCGCTCTAGGCCCCAGGGCCT TACGGAGGCCGAGCAGCGGGAGCTGGAGCAAGAGGCCAAAGAACTGAAGAAGG TGATGGATCTGAGTATAGTGCGGCTGCGCTTCTCTGCCTTCCTTAGAGCCAGTGAT GGCTCCTTCTCCCTGCCCCTGAAGCCAGTCATCTCCCAGCCCATCCATGACAGCAA ATCTCCGGGGGCATCAAACCTGAAGATTTCTCGAATGGACAAGACAGCAGGCTCT GTGCGGGGTGGAGATGAAGTTTATCTGCTTTGTGACAAGGTGCAGAAAGATGACA TTGAGGTTCGGTTCTATGAGGATGATGAGAATGGATGGCAGGCCTTTGGGGACTTC TCTCCCACAGATGTGCATAAACAGTATGCCATTGTGTTCCGGACACCCCCCTATCA CAAGATGAAGATTGAGCGGCCTGTAACAGTGTTTCTGCAACTGAAACGCAAGCGA GGAGGGGACGTGTCTGATTCCAAACAGTTCACCTATTACCCTCTGGTGGAAGACA AGGAAGAGGTGCAGCGGAAGCGGAGGAAGGCCTTGCCCACCTTCTCCCAGCCCT TCGGGGGTGGCTCCCACATGGGTGGAGGCTCTGGGGGTGCAGCCGGGGGCTACG GAGGAGCTGGAGGAGGTGGCAGCCTCGGTTTCTTCCCCTCCTCCCTGGCCTACAG CCCCTACCAGTCCGGCGCGGGCCCCATGGGCTGCTACCCGGGAGGCGGGGGCGG GGCGCAGATGGCCGCCACGGTGCCCAGCAGGGACTCCGGGGAGGAAGCCGCGGA GCCAAGCGCCCCCTCCAGGACCCCCCAGTGCGAGCCGCAGGCCCCGGAGATGCT GCAGCGAGCTCGAGAGTACAACGCGCGCCTGTTCGGCCTGGCGCAGCGCAGCGC CCGAGCCCTACTCGACTACGGCGTCACCGCGGACGCGCGCGCGCTGCTGGCGGG ACAGCGCCACCTGCTGACGGCGCAGGACGAGAACGGAGACACACCACTGCACCT AGCCATCATCCACGGGCAGACCAGTGTCATTGAGCAGATAGTCTATGTCATCCACC ACGCCCAGGACCTCGGCGTTGTCAACCTCACCAACCACCTGCACCAGACGCCCCT GCACCTGGCGGTGATCACGGGGCAGACGAGTGTGGTGAGCTTTCTGCTGCGGGTA GGTGCAGACCCAGCTCTGCTGGATCGGCATGGAGACTCAGCCATGCATCTGGCGC TGCGGGCAGGCGCTGGTGCTCCTGAGCTGCTGCGTGCACTGCTTCAGAGTGGAGC TCCTGCTGTGCCCCAGCTGTTGCATATGCCTGACTTTGAGGGACTGTATCCAGTAC ACCTGGCAGTCCGAGCCCGAAGCCCTGAGTGCCTGGATCTGCTGGTGGACAGTGG GGCTGAAGTGGAGGCCACAGAGCGGCAGGGGGGACGAACAGCCTTGCATCTAGC CACAGAGATGGAGGAGCTGGGGTTGGTCACCCATCTGGTCACCAAGCTCCGGGCC AACGTGAACGCTCGCACCTTTGCGGGAAACACACCCCTGCACCTGGCAGCTGGA CTGGGGTACCCGACCCTCACCCGCCTCCTTCTGAAGGCTGGTGCTGACATCCATGC TGAAAACGAGGAGCCCCTGTGCCCACTGCCTTCACCCCCTACCTCTGATAGCGAC TCGGACTCTGAAGGGCCTGAGAAGGACACCCGAAGCAGCTTCCGGGGCCACACG CCTCTTGACCTCACTTGCAGCACCAAGGTGAAGACCTTGCTGCTAAATGCTGCTC-90-4927-7786-8905.2Atty. Dkt. No.: 121384-0285AGAACACCATGGAGCCACCCCTGACCCCGCCCAGCCCAGCAGGGCCGGGACTGTCACTTGGTGATACAGCTCTGCAGAACCTGGAGCAGCTGCTAGACGGGCCAGAAGCCCAGGGCAGCTGGGCAGAGCTGGCAGAGCGTCTGGGGCTGCGCAGCCTGGTAGACACGTACCGACAGACAACCTCACCCAGTGGCAGCCTCCTGCGCAGCTACGAGCTGGCTGGCGGGGACCTGGCAGGTCTACTGGAGGCCCTGTCTGACATGGGCCTAGAGGAGGGAGTGAGGCTGCTGAGGGGTCCAGAAACCCGAGACAAGCTGCCCAGCACAGCAGAGGTGAAGGAAGACAGTGCGTACGGGAGCCAGTCAGTGGAGCAGGAGGCAGAGAAGCTGGGCCAACCCCCTGAGCCACCAGGAGGGCTCTGCCACGGGCACCCCCAGCCTCAGGTGCACTGA> SEQ ID NO: 27> RASGRP1 M261I> Length: 2391 nucleotidesATGGGCACCCTGGGCAAGGCGAGAGAGGCTCCGCGGAAACCTTCCCATGGCTGCAGAGCTGCCTCTAAAGCAAGACTAGAGGCAAAGCCAGCCAACAGCCCCTTCCCCTCCCATCCCAGCTTGGCCCACATCACCCAGTTCCGAATGATGGTGTCTCTGGGACATTTAGCCAAAGGAGCCAGCCTGGACGATCTCATTGACAGCTGCATTCAATCTTTTGATGCAGATGGAAACCTGTGTCGAAGTAACCAACTGTTGCAAGTCATGCTGACCATGCACCGAATTGTCATCTCCTCTGCAGAACTGCTCCAAAAAGTTATCACCCTCTATAAGGATGCTTTGGCAAAGAATTCACCAGGACTTTGCCTGAAGATCTGTTATTTTGTAAGGTATTGGATAACAGAATTCTGGGTCATGTTTAAAATGGACGCCAGCTTGACAGACACTATGGAGGAGTTTCAGGAACTGGTGAAAGCTAAGGGTGAGGAGTTACATTGCCGCCTGATTGACACAACTCAAATCAATGCCCGTGACTGGTCCAGGAAACTTACTCAAAGGATAAAATCAAATACCAGCAAGAAACGGAAAGTCTCCCTGCTCTTTGACCATCTGGAACCAGAAGAGCTATCCGAGCACCTCACCTACCTTGAGTTCAAGTCTTTCCGGAGGATATCGTTCTCTGATTATCAGAATTACCTTGTAAATAGCTGTGTGAAGGAAAACCCCACCATGGAGCGATCTATTGCTCTGTGCAACGGCATCTCCCAGTGGGTACAACTGATCGTTCTCAGCCGCCCCACGCCGCAGCTCCGAGCAGAAGTCTTCATCAAGTTCATCCAGGTGGCTCAGAAGCTCCACCAACTACAGAACTTCAATACACTGATGGCTGTGATAGGTGGGCTGTGTCACAGCTCAATCTCGAGGCTCAAGGAGACAAGTTCGCATGTCCCACATGAAATCAATAAGGTTCTCGGTGAGATGACTGAGCTGCTGTCCTCCTCCAGAAACTACGACAATTACCGGCGAGCCTATGGAGAGTGCACCGACTTCAAGATCCCCATTCTGGGTGTGCATCTCAAGGACCTCATCTCCCTGTATGAAGCCATGCCTGACTATCTGGAGGACGGGAAAGTGAACGTCCATAAGCTACTGGCCCTATACAATCATATCAGTGAATTGGTCCAGCTGCAAGAGGTGGCCCCACCCTTGGAGGCTAACAAGGACTTGGTACACTTGCTGACGTTATCCCTGGATCTTTACTACACTGAGGATGAAATCTATGAGCTTTCCTATGCCCGGGAACCAAGGAACCACAGAGCTCCACCACTAACACCTTCAAAGCCACCAGTAGTAGTGGACTGGGCTTCTGGAGTGTCTCCCAAACCTGATCCAAAAACCATTAGCAAACACGTCCAGAGGATGGTGGATTCTGTCTTCAAGAACTATGATCACGACCAGGATGGATACATTTCTCAGGAAGAATTTGAAAAGATTGCTGCGAGTTTTCCATTTTCCTTCTGTGTGATGGACAAAGACAGGGAAGGCCTCATCAGCAGGGATGAGATCACAGCCTACTTCATGAGAGCCAGCTCAATCTATTCCAAGCTGGGCCTGGGCTTTCCTCACAACTTCCAAGAGACCACCTACCTGAAGCCCACTTTTT-91-4927-7786-8905.2Atty. Dkt. No.: 121384-0285GTGACAACTGTGCTGGATTTCTCTGGGGAGTGATCAAACAAGGATATCGATGTAAAGACTGCGGGATGAACTGTCACAAACAATGCAAAGATCTGGTTGTGTTTGAGTGTAAGAAGCGAGCCAAGAACCCAGTAGCTCCCACAGAGAACAACACTTCTGTGGGGCCAGTGTCCAACCTTTGCTCATTGGGAGCCAAAGATCTGCTCCATGCACCTGAGGAAGGACCTTTTACATTCCCTAATGGGGAGGCTGTGGAACATGGTGAGGAGAGTAAGGATCGGACCATCATGCTGATGGGAGTGTCCTCACAGAAGATTTCTCTTCGGCTGAAGAGGGCTGTTGCCCACAAGGCCACCCAGACTGAATCACAGCCTTGGATTGGCAGTGAGGGCCCTTCAGGTCCCTTTGTGCTGTCTTCCCCAAGGAAGACAGCCCAGGATACTCTATATGTGCTTCCCAGTCCCACCTCTCCATGTCCTAGCCCAGTCTTGGTCAGAAAGCGGGCTTTTGTCAAGTGGGAGAATAAAGACTCCCTCATAAAATCAAAGGAGGAGCTCCGTCACCTCAGACTGCCTACCTACCAAGAACTGGAACAGGAAATAAATACTCTGAAAGCAGATAATGATGCCCTAAAGATCCAACTGAAATATGCACAGAAGAAAATAGAATCCCTCCAGCTTGAAAAAAGCAATCATGTCTTAGCTCAAATGGAGCAGGGTGACTGTTCT> SEQ ID NO: 28> AKT1 E17K> Length: 1440 nucleotidesATGAGCGACGTGGCTATTGTGAAGGAGGGTTGGCTGCACAAACGAGGGAAGTACATCAAGACCTGGCGGCCACGCTACTTCCTCCTCAAGAATGATGGCACCTTCATTGGCTACAAGGAGCGGCCGCAGGATGTGGACCAACGTGAGGCTCCCCTCAACAACTTCTCTGTGGCGCAGTGCCAGCTGATGAAGACGGAGCGGCCCCGGCCCAACACCTTCATCATCCGCTGCCTGCAGTGGACCACTGTCATCGAACGCACCTTCCATGTGGAGACTCCTGAGGAGCGGGAGGAGTGGACAACCGCCATCCAGACTGTGGCTGACGGCCTCAAGAAGCAGGAGGAGGAGGAGATGGACTTCCGGTCGGGCTCACCCAGTGACAACTCAGGGGCTGAAGAGATGGAGGTGTCCCTGGCCAAGCCCAAGCACCGCGTGACCATGAACGAGTTTGAGTACCTGAAGCTGCTGGGCAAGGGCACTTTCGGCAAGGTGATCCTGGTGAAGGAGAAGGCCACAGGCCGCTACTACGCCATGAAGATCCTCAAGAAGGAAGTCATCGTGGCCAAGGACGAGGTGGCCCACACACTCACCGAGAACCGCGTCCTGCAGAACTCCAGGCACCCCTTCCTCACAGCCCTGAAGTACTCTTTCCAGACCCACGACCGCCTCTGCTTTGTCATGGAGTACGCCAACGGGGGCGAGCTGTTCTTCCACCTGTCCCGGGAGCGTGTGTTCTCCGAGGACCGGGCCCGCTTCTATGGCGCTGAGATTGTGTCAGCCCTGGACTACCTGCACTCGGAGAAGAACGTGGTGTACCGGGACCTCAAGCTGGAGAACCTCATGCTGGACAAGGACGGGCACATTAAGATCACAGACTTCGGGCTGTGCAAGGAGGGGATCAAGGACGGTGCCACCATGAAGACCTTTTGCGGCACACCTGAGTACCTGGCCCCCGAGGTGCTGGAGGACAATGACTACGGCCGTGCAGTGGACTGGTGGGGGCTGGGCGTGGTCATGTACGAGATGATGTGCGGTCGCCTGCCCTTCTACAACCAGGACCATGAGAAGCTTTTTGAGCTCATCCTCATGGAGGAGATCCGCTTCCCGCGCACGCTTGGTCCCGAGGCCAAGTCCTTGCTTTCAGGGCTGCTCAAGAAGGACCCCAAGCAGAGGCTTGGCGGGGGCTCCGAGGACGCCAAGGAGATCATGCAGCATCGCTTCTTTGCCGGTATCGTGTGGCAGCACGTGTACGAGAAGAAGCTCAGCCCACCCTTCAAGCCCCAGGTCACGTCGGAGACTGACACCAGGTATTTTGATGAGGAGTTCACGGCCCAGATGATCACCATCACACCACCTGACCAAGATGACAG-92-4927-7786-8905.2Atty. Dkt. No.: 121384-0285CATGGAGTGTGTGGACAGCGAGCGCAGGCCCCACTTCCCCCAGTTCTCCTACTCGGCCAGCGGCACGGCC> SEQ ID NO: 29> MAPK1 D321G> Length: 1080 nucleotidesATGGCGGCGGCGGCGGCGGCGGGCGCGGGCCCGGAGATGGTCCGCGGGCAGGTGTTCGACGTGGGGCCGCGCTACACCAACCTCTCGTACATCGGCGAGGGCGCCTACGGCATGGTGTGCTCTGCTTATGATAATGTCAACAAAGTTCGAGTAGCTATCAAGAAAATCAGCCCCTTTGAGCACCAGACCTACTGCCAGAGAACCCTGAGGGAGATAAAAATCTTACTGCGCTTCAGACATGAGAACATCATTGGAATCAATGACATTATTCGAGCACCAACCATCGAGCAAATGAAAGATGTATATATAGTACAGGACCTCATGGAAACAGATCTTTACAAGCTCTTGAAGACACAACACCTCAGCAATGACCATATCTGCTATTTTCTCTACCAGATCCTCAGAGGGTTAAAATATATCCATTCAGCTAACGTTCTGCACCGTGACCTCAAGCCTTCCAACCTGCTGCTCAACACCACCTGTGATCTCAAGATCTGTGACTTTGGCCTGGCCCGTGTTGCAGATCCAGACCATGATCACACAGGGTTCCTGACAGAATATGTGGCCACACGTTGGTACAGGGCTCCAGAAATTATGTTGAATTCCAAGGGCTACACCAAGTCCATTGATATTTGGTCTGTAGGCTGCATTCTGGCAGAAATGCTTTCTAACAGGCCCATCTTTCCAGGGAAGCATTATCTTGACCAGCTGAACCACATTTTGGGTATTCTTGGATCCCCATCACAAGAAGACCTGAATTGTATAATAAATTTAAAAGCTAGGAACTATTTGCTTTCTCTTCCACACAAAAATAAGGTGCCATGGAACAGGCTGTTCCCAAATGCTGACTCCAAAGCTCTGGACTTATTGGACAAAATGTTGACATTCAACCCACACAAGAGGATTGAAGTAGAACAGGCTCTGGCCCACCCATATCTGGAGCAGTATTACGACCCGAGTGGCGAGCCCATCGCCGAAGCACCATTCAAGTTCGACATGGAATTGGATGACTTGCCTAAGGAAAAGCTCAAAGAACTAATTTTTGAAGAGACTGCTAGA TTCCAGCCAGGATACAGATCT> SEQ ID NO: 30> KHDRBS1-LCK Fusion> Length: 2046ATGCAACGTCGGGATGATCCTGCGGCGAGAATGTCTCGCAGCTCCGGGCGCAGTGGGAGCATGGACCCCTCTGGGGCGCACCCTAGTGTGAGGCAGACACCATCCAGGCAACCCCCACTGCCTCATCGCTCTCGCGGCGGGGGCGGTGGGTCTAGGGGCGGAGCGCGAGCCTCACCCGCTACCCAGCCTCCTCCTCTCTTACCTCCGAGCGCTACTGGTCCCGATGCTACAGTTGGCGGGCCTGCCCCAACCCCTCTGCTGCCACCTTCCGCTACCGCATCTGTGAAGATGGAGCCTGAGAACAAATACCTGCCAGAGCTGATGGCTGAAAAGGATAGCCTTGACCCTTCTTTCACACATGCTATGCAGCTGCTGACAGCAGAGATCGAGAAAATTCAGAAGGGGGATAGCAAGAAGGACGATGAAGAAAACTACCTGGAC-93-4927-7786-8905.2Atty. Dkt. No.: 121384-0285CTCTTTAGTCACAAAAATATGAAACTCAAGGAGAGGGTGCTGATTCCTGTCAAAC AGTATCCGAAGTTCAACTTCGTTGGGAAGATCCTGGGCCCTCAAGGTAATACCATC AAGAGACTGCAGGAGGAGACCGGCGCGAAGATCTCTGTCCTGGGTAAAGGGAGCATGAGGGACAAAGCCAAGCTCCTGATCCGGAACGGGAGCGAGGTGAGAGATCCTCTCGTGACCTACGAAGGGAGTAACCCACCAGCAAGTCCCCTTCAGGATAATTTGG TGATAGCGCTCCATAGCTATGAACCAAGCCATGATGGGGACCTGGGCTTTGAAAA AGGGGAGCAACTCAGAATCTTAGAACAGTCAGGAGAGTGGTGGAAGGCACAGTCATTAACTACTGGGCAAGAAGGGTTCATTCCTTTTAACTTCGTGGCCAAGGCCAATT CACTCGAACCGGAGCCATGGTTTTTTAAAAACTTGAGTAGGAAAGACGCAGAGCG CCAGCTCCTCGCGCCCGGTAACACCCACGGCAGTTTCCTGATTCGCGAGAGCGAATCAACGGCCGGAAGCTTTTCCCTGAGTGTTCGGGATTTTGATCAGAACCAAGGTG AAGTGGTAAAGCATTATAAGATTCGCAACCTGGATAACGGCGGTTTTTATATCAGT CCCCGGATCACCTTTCCCGGGCTTCATGAGCTCGTCAGGCATTACACAAATGCTTCAGATGGCCTTTGTACCCGACTGTCCAGACCATGTCAAACTCAGAAGCCACAGAAACCATGGTGGGAGGACGAGTGGGAGGTGCCCCGCGAGACACTCAAATTGGTGGAGCGGCTCGGGGCTGGCCAATTTGGAGAGGTGTGGATGGGCTATTATAACGGACACACCAAAGTGGCCGTGAAGTCTCTCAAACAGGGATCTATGAGCCCCGACGCTTTCCTGGCCGAGGCCAATCTGATGAAGCAGCTTCAACACCAAAGACTGGTGAGGTTGTATGCTGTGGTAACCCAAGAGCCCATTTATATTATTACTGAGTACATGGAAAACGGCAGCCTCGTCGATTTCCTGAAAACTCCCAGCGGTATCAAATTGACTATAAACAAACTCCTGGATATGGCGGCCCAGATCGCTGAAGGGATGGCCTTCATCGAGGAAAGGAACTATATTCATCGAGATCTGAGAGCCGCAAATATATTGGTGAGCGACACCCTGTCTTGCAAGATTGCTGATTTTGGGTTGGCCAGATTGATTGAAGACAATGAGTACACCGCTCGGGAGGGGGCAAAGTTTCCAATCAAGTGGACCGCCCCGGAGGCCATTAATTACGGGACCTTTACCATCAAGAGCGATGTGTGGAGCTTCGGAATTCTTCTCACTGAAATCGTG ACACACGGACGCATCCCATATCCTGGGATGACAAACCCAGAAGTCATTCAGAATC TTGAGAGAGGTTATCGCATGGTCCGGCCCGATAACTGTCCGGAGGAGTTATATCAGTTGATGCGACTCTGTTGGAAAGAACGCCCCGAGGATAGACCCACTTTCGATTATTT GAGGAGCGTGTTGGAGGACTTTTTCACAGCTACGGAAGGCCAGTACCAGCCCCA GCCA> SEQ ID NO: 31> VAV1 -MYO IF Fusion> Length: 2856ATGGAACTGTGGCGGCAGTGCACCCACTGGCTGATTCAGTGTCGAGTGCTGCCTCCTAGCCACCGGGTGACCTGGGACGGCGCCCAGGTGTGCGAGCTGGCTCAGGCCCTGAGAGATGGCGTGCTGCTCTGCCAGCTGCTTAACAACCTGCTGCCTCACGCCATCAACCTGAGAGAGGTCAACCTGAGACCCCAGATGTCTCAGTTCCTGTGCCTGAAGAACATCAGAACCTTCCTGAGCACCTGTTGCGAGAAGTTCGGCCTGAAGCGATCTGAGCTGTTCGAGGCTTTCGATCTGTTCGATGTGCAGGACTTCGGCAAGGTGATCTACACCCTGAGCGCCCTGAGCTGGACCCCTATCGCCCAGAACAGAGGCATTATGCCATTCCCCACCGAGGAAGAGAGCGTGGGCGACGAGGATATCTACAGCGGCCTGTCTGACCAGATCGACGACACCGTGGAAGAAGACGAGGACCTCTACGATTGCGTGGAAAA-94-4927-7786-8905.2Atty. Dkt. No.: 121384-0285CGAGGAGGCCGAAGGCGACGAAATCTATGAGGACCTGATGAGGAGCGAACCCGTGTCCATGCCTCCTAAGATGACCGAGTACGACAAGCGGTGTTGCTGCCTGCGGGAAATCCAGCAGACCGAGGAAAAGTACACAGACACCCTGGGCAGCATCCAACAGCACTTTCTGAAGCCTCTGCAGAGATTCCTTAAACCCCAAGATATCGAAATCATCTTCATCAACATCGAGGACCTGCTGCGGGTGCACACCCACTTCCTGAAGGAGATGAAGGAAGCTCTGGGAACCCCTGGCGCCGCCAACCTGTACCAGGTGTTCATCAAATACAAGGAACGGTTCCTGGTCTACGGCCGGTACTGCAGCCAGGTTGAGAGCGCCTCCAAGCACCTGGATAGAGTGGCCGCTGCTAGAGAGGACGTGCAGATGAAACTGGAAGAATGCAGCCAGAGAGCGAACAACGGCAGATTCACCCTGAGAGATCTGCTGATGGTGCCAATGCAACGGGTGCTGAAATATCACCTGCTGCTGCAGGAGCTAGTGAAACATACCCAGGAGGCGATGGAAAAGGAGAACCTGAGACTGGCCCTGGACGCCATGAGAGATCTGGCCCAATGTGTCAATGAGGTAAAGAGAGACAACGAGACACTGCGGCAGATCACCAACTTCCAGCTGAGCATCGAGAACCTGGACCAGAGCCTGGCCCACTACGGACGGCCAAAGATCGATGGCGAGCTCAAGATCACCAGCGTGGAAAGAAGAAGCAAGATGGACAGATACGCCTTTCTGCTGGACAAGGCACTGCTGATTTGCAAGAGAAGAGGCGACAGCTACGACCTGAAGGATTTTGTGAACCTGCACTCTTTCCAGGTGCGGGATGACAGCAGCGGCGACAGAGATAACAAGAAGTGGTCCCACATGTTCCTCCTGATCGAGGACCAGGGCGCTCAAGGATACGAGCTGTTCTTCAAGACCAGAGAGCTGAAGAAAAAATGGATGGAGCAGTTTGAGATGGCAATCAGCAACATCTACCCCGAGAACGCCACAGCCAATGGCCACGACTTCCAGATGTTCAGCTTCGAGGAAACGACCAGCTGCAAGGCCTGCCAGATGCTGCTGCGGGGCACATTCTATCAGGGCTACCGGTGTCACAGATGTAGAGCCAGTGCCCATAAGGAATGTCTGGGACGGGTCCCCCCCTGCGGCAGACACGGCCAGGACTTCCCCGGCACCATGAAGAAAGATAAGCTGCACCGGCGGGCCCAGGACAAGAAGAGAAATGAGCTGGGCCTGCCTAAGATGGAAGTGTTTCAGGAGTACTACGGCCTGCCTCCTCCCCCTGGCGCTATCGGCCCTTTCCTGCGGCTGAATCCTGGAGATATCGTGGAGTTGACAAAGGCCGAGGCCGAACAGAATTGGTGGGAGGGCAGAAACACCTCTACAAACGAAATCGGCTGGTTCCCATGCAACAGAGTTAAGCCCTACGTGCACGGCCCTCCTCAGGATCTGAGCGTGCACCTGTGGTATGCCGGACCTATGGAGCGGGCCGGCGCCGAGAGCATCCTGGCCAACCGGTCCGATGGAACATTTCTGGTGCGGCAGAGAGTGAAAGACGCCGCTGAATTCGCCATCAGCATCAAGTACAACGTTGAAGTGAAGCACATCAAAATCATGACCGCCGAGGGCCTGTATAGAATCACAGAAAAAAAAGCCTTCAGAGGCCTGACCGAGCTGGTGGAGTTCTACCAGCAAAATTCTCTGAAGGACTGCTTCAAGAGCCTGGATACAACGCTGCAATTTCCTTTCAAAGAGCCTGAGAAAAGAACAATCAGCAGACCCGCCGAACCTACCAGAAAGGGCATGGCCAAGGGCAAGCCGCGGCGGTCCTCCCAGGCCCCTACAAGAGCTGCTCCTGCCCCTCCTCGAGGCATGGACAGAAACGGCGTGCCCCCATCTGCCCGGGGCGGTCCACTGCCCCTGGAAATCATGAGCGGCGGCGGCACACACCGGCCACCTAGAGGACCTCCTAGCACCAGCCTGGGCGCCTCCAGACGCCCCAGAGCCAGACCCCCATCTGAGCACAACACCGAGTTTCTGAACGTGCCTGACCAGGGCATGGCCGGCATGCAGAGAAAGAGAAGCGTGGGCCAAAGACCTGTGCCCGGAGTGGGACGCCCTAAGCCTCAGCCTAGAACACACGGCCCTAGATGCAGAGCCCTGTACCAGTACGTGGGCCAGGACGTGGACGAGCTGAGCTTTAACGTGAACGAAGTGATCGAGATCCTGATGGAAGACCCCTCCGGATGGTGGAAGGGACGCCTCCATGGCCAAGAGGGACTGTTTCCAGGGAATTACGTGGAAAAGATT-95-4927-7786-8905.2Atty. Dkt. No.: 121384-0285> SEQ ID NO: 32> FYN-TRAF3IP2 Fusion> Length: 750 amino acidsMGCVQCKDKEATKLTEERDGSLNQSSGYRYGTDPTPQHYPSFGVTSIPNYNNFHAAG GQGLTVFGGVNS S SHTGTLRTRGGTGVTLF VALYDYEARTEDDLSFHKGEKFQILNS S EGDWWEARSLTTGETGYIPSNYVAPVDSIQAEEWYFGKLGRKDAERQLLSFGNPRGT FLIRESETTKETRMNRSIPVEVDESEPYPSQLLKPIPEYSPEEESEPPAPNIRNMAPNSLS APTMLHNSSGDFSQAHSTLKLANHQRPVSRQVTCLRTQVLEDSEDSFCRRHPGLGKA FPSGCSAVSEPASESVVGALPAEHQFSFMEKRNQWLVSQLSAASPDTGHDSDKSDQSL PNASADSLGGSQEMVQRPQPHRNRAGLDLPTIDTGYDSQPQDVLGIRQLERPLPLTSV CYPQDLPRPLRSREFPQFEPQRYPACAQMLPPNLSPHAPWNYHYHCPGSPDHQVPYG HDYPRAAYQQVIQPALPGQPLPGASVRGLHPVQKVILNYPSPWDHEERPAQRDCSFP GLPRHQDQPHHQPPNRAGAPGESLECPAELRPQVPQPPSPAAVPRPPSNPPARGTLKTS NLPEELRKVFITYSMDTAMEVVKFVNFLLVNGFQTAIDIFEDRIRGIDIIKWMERYLRD KTVMIIVAISPKYKQDVEGAESQLDEDEHGLHTKYIHRMMQIEFIKQGSMNFRFIPVL FPNAKKEHVPTWLQNTHVYSWPKNKKNILLRLLREEEYVAPPRGPLPTLQVVPLSEQ ID NO: 33VAV1-STAP2 Fusion> Length: 904 amino acidsMELWRQCTHWLIQCRVLPPSHRVTWDGAQVCELAQALRDGVLLCQLLNNLLPHAIN LREVNLRPQMSQFLCLKNIRTFLSTCCEKFGLKRSELFEAFDLFDVQDFGKVIYTLSA LSWTPIAQNRGIMPFPTEEESVGDEDIYSGLSDQIDDTVEEDEDLYDCVENEEAEGDEIYEDLMRSEPVSMPPKMTEYDKRCCCLREIQQTEEKYTDTLGSIQQHFLKPLQRFLKP QDIEIIFINIEDLLRVHTHFLKEMKEALGTPGAANLYQVFIKYKERFLVYGRYCSQVESASKHLDRVAAAREDVQMKLEECSQRANNGRFTLRDLLMVPMQRVLKYHLLLQELV I<HTQEAMEI<ENLRLALDAMRDLAQCVNEVI<RDNETLRQITNFQLSIENLDQSLAHYGRPKIDGELKITSVERRSKMDRYAFLLDKALLICKRRGDSYDLKDFVNLHSFQVRDD SSGDRDNKKWSHMFLLIEDQGAQGYELFFKTRELKKKWMEQFEMAISNIYPENATA NGHDFQMFSFEETTSCKACQMLLRGTFYQGYRCHRCRASAHKECLGRVPPCGRHGQ DFPGTMKKDKLHRRAQDKKRNELGLPKMEVFQEYYGLPPPPGAIGPFLRLNPGDIVE LTKAEAEQNWWEGRNTSTNEIGWFPCNRVKPYVHGPPQDLSVHLWYAGPMERAGA ESILANRSDGTFLVRQRVKDAAEFAISIKYNVEVKHIKIMTAEGLYRITEKKAFRGLTE LVEFYQQNSLKDCFKSLDTTLQFPFKEPEKRTISRPAGPAPCTGGPKPLSPASSQDKLPP LPPLPNQEENYVTPIGDGPAVDYENQDVASSSWPVILKPKKLPKPPAKLPKPPVGPKPE PKVFNGGLGRKLPVSSAQPLFPTAGLADMTAELQKKLEKRRALEH> SEQ ID NO: 344927-7786-8905.2Atty. Dkt. No.: 121384-0285> CAPRIN-JAK2 Fusion> Length: 988 amino acidsMPSATSHSGSGSKSSGPPPPSGSSGSEAAAGAGAAAPASQHPATGTGAVQTEAMKQIL GVIDKKLRNLEKKKGKLDDYQERMNKGERLNQDQLDAVSKYQEVTNNLEFAKELQ RSFMALSQDIQKTIKKTARREQLMREEAEQKRLKTVLELQYVLDKLGDDEVRTDLK QGLNGVPILSEEELSLLDEFYKLVDPERDMSLRLNEQYEHASIHLWDLLEGKEKPVCG TTYKVLKEIVERVFQSNYFDSTHNHQNGLCEEEEAASAPAVEDQVPEAEPEPAEEYTE QSEVESTEYVNRQFMAETQFTSGEKEQVDEWTVETVEVVNSLQQQPQAASPSVPEP HSLTPVAQADPLVRRQRVQDLMAQMQGPYNFIQDSMLDFENQTLDPAIVSAQPMNPT QNMDMPQLVCPPVHSESRLAQPNQVPVQPEATQVPLVSSTSEGYTASQPLYQPSHATE QRPQKEPIDQIQ ATISLNTDQTTAS S SLPAASQPQVFQ AGTSKPLHS SGINVNAAPFQ S MQTVFNMNAPVPPVNEPETLKQQNQYQASYNQSFSSQPHQVEQTELQQEQLQTLQE RIPWVPPECIENPKNLNLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQL PAPKWAELANLINNCMDYEPDFRPSFRAIIRDLNSLFTPDYELLTENDMLPNMRIGAL GFSGAFEDRDPTQFEERHLKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQH STEEHLRDFEREIEILKSLQHDNIVKYKGVCYSAGRRNLKLIMEYLPYGSLRDYLQKH KERIDHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQ DKEYYKVKEPGESPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYIEKSKSPPAEFMRMIGNDKQGQMIVFHLIELLKNNGRLPRPDGCPDEIYMIMTECWNNNVNQRPSFRDL ALRVDQIRDNMA> SEQ ID NO: 35> mCTLA4-mCD28 Fusion> Length: 231 amino acidsMACLGLRRYKAQLQLPSRTWPFVALLTLLFIPVFSEAIQVTQPSVVLASSHGVASFPCEYSPSHNTDEVRVTVLRQTNDQMTEVCATTFTEKNTVGFLDYPFCSGTFNESRVNLTIQGLRAVDTGLYLCKVELMYPPPYFVGMGNGTQIYVIDPEPCPDSDFLLWILVAVSLGLFFYSFLVSAVSLSKMTNSRRNRLLQSDYMNMTPRRPGLTRKPYQPYAPARDFAAYRP> SEQ ID NO: 36> IKZF2-ERBB4 Fusion> Length: 1292 amino acidsMETEAIDGYITVCAGTENKLSSLSDLEQQYRALRKYYENCEVVMGNLEITSIEHNRDLSFLRSVREVTGYVLVALNQFRYLPLENLRIIRGTKLYEDRYALAIFLNYRKDGNFGLQELGLKNLTEILNGGVYVDQNKFLCYADTIHWQDIVRNPWPSNLTLVSTNGSSGCGRCHKSCTGRCWGPTENHCQTLTRTVCAEQCDGRCYGPYVSDCCHRECAGGCSGPKDT-97-4927-7786-8905.2Atty. Dkt. No.: 121384-0285DCFACMNFNDSGACVTQCPQTFVYNPTTFQLEHNFNAKYTYGAFCVKKCPHNFVVD S S SC VRACPS SKMEVEENGIKMCKPCTDICPKACDGIGTGSLMS AQTVD SSNIDKFIN CTKINGNLIFLVTGIHGDPYNAIEAIDPEKLNVFRTVREITGFLNIQSWPPNMTDFSVFS NLVTIGGRVLYSGLSLLILKQQGITSLQFQSLKEISAGNIYITDNSNLCYYHTINWTTLF STINQRIVIRDNRKAENCTAEGMVCNHLCSSDGCWGPGPDQCLSCRRFSRGRICIESC NLYDGEFREFENGSICVECDPQCEKMEDGLLTCHGPGPDNCTKCSHFKDGPNCVEKC PDGLQGANSFIFKYADPDRECHPCHPNCTQGCNGPTSHDCIYYPWTGHSTLPQHART PLIAAGVIGGLFILVIVGLTFAVYVRRKSIKKKRALRRFLETELVEPLTPSGTAPNQAQL RILKETELKRVKVLGSGAFGTVYKGIWVPEGETVKIPVAIKILNETTGPKANVEFMDE ALIMASMDHPHLVRLLGVCLSPTIQLVTQLMPHGCLLEYVHEHKDNIGSQLLLNWCV QIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLEGDEKEYNADGGK MPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGER LPQPPICTID VYMVMVKCWMIDAD SRPKFKEL AAEF SRMARDPQRYLVIQGDDRMK LPSPNDSKFFQNLLDEEDLEDMMDAEEYLVPQAFNIPPPIYTSRARIDSNRSEIGHSPPP AYTPMSGNQFVYRDGGFAAEQGVSVPYRAPTSTIPEAPVAQGATAEIFDDSCCNGTLR KPVAPHVQEDSSTQRYSADPTVFAPERSPRGELDEEGYMTPMRDKPKQEYLNPVEEN PFVSRRKNGDLQALDNPEYHNASNGPPKAEDEYVNEPLYLNTFANTLGKAEYLKNNI LSMPEKAKKAFDNPDYWNHSLPPRSTLQHPDYLQEYSTKYFYKQNGRIRPIVAENPE YLSEFSLKPGTVLPPPPYRHRNTVV> SEQ ID NO: 37> PABPC1-TYK2 Fusion> Length: 717 amino acidsMNPSAPSYPMASLYVGDLHPDVTEAMLYEKFSPAGPILSIRVCRDMITRRSLGYAYVNFQQPADAERALDTMNFDVIKGKPVRIMWSQRDPSLRKSGVGNIFIKNLDKSIDNKALYDTFSAFGNILSCKVVCDENGSKGYGFVHFETQEAAERAIEKMNGMLLNDRKVFVGRFKSRKEREAELGARAKEFTNVYIKNFGEDMDDERLKDLFGKFGPALSVKVMTDESGKSKGFGFVSFERHEDAQKAVDEMNGKELNGKQIYVGRAQKKVERQTELKRKFEQMKQDRITRYQGVNLYVKNLDDGIDDERLRKEFSPFGTITSAKMDKWGFGATLLEICFDGEAPLQSRSPSEKEHFYQRQHRLPEPSCPQLATLTSQCLTYEPTQRPSFRTILRDLTRLQPHNLADVLTVNPDSPASDPTVFHKRYLKKIRDLGEGHFGKVSLYCYDPTNDGTGEMVAVKALKADCGPQHRSGWKQEIDILRTLYHEHIIKYKGCCEDQGEKSLQLVMEYVPLGSLRDYLPRHSIGLAQLLLFAQQICEGMAYLHAQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVPEGHEYYRVREDGDSPVFWYAPECLKEYKFYYASDVWSFGVTLYELLTHCDSSQSPPTKFLELIGIAQGQMTVLRLTELLERGERLPRPDKCPCEVYHLMKNCWETEASFRPTFENLIPILKTVHEKYQGQAPSVFSVC> SEQ ID NO: 38> mCD3E S34C4927-7786-8905.2Atty. Dkt. No.: 121384-0285> Length: 189 amino acidsMRWNTFWGILCLSLLAVGTCQDDAENIEYKVSICGTSVELTCPLDSDENLKWEKNGQELPQKHDKHLVLQDFSEVEDSGYYVCYTPASNKNTYLYLKARVCEYCVEVDLTAVAIIIIVDICITLGLLMVIYYWSKNRKAKAKPVTRGTGAGSRPRGQNKERPPPVPNPDYEPIRKGQRDLYSGLNQRAV> SEQ ID NO: 39> KHDRBS1-LCK Fusion> Length: 682 amino acidsMQRRDDPAARMSRSSGRSGSMDPSGAHPSVRQTPSRQPPLPHRSRGGGGGSRGGARASPATQPPPLLPPSATGPDATVGGPAPTPLLPPSATASVKMEPENKYLPELMAEKDSLDPSFTHAMQLLTAEIEKIQKGDSKKDDEENYLDLFSHKNMKLKERVLIPVKQYPKFNFVGKILGPQGNTIKRLQEETGAKISVLGKGSMRDKAKLLIRNGSEVRDPLVTYEGSNPPASPLQDNLVIALHSYEPSHDGDLGFEKGEQLRILEQSGEWWKAQSLTTGQEGFIPFNFVAKANSLEPEPWFFKNLSRKDAERQLLAPGNTHGSFLIRESESTAGSFSLSVRDFDQNQGEVVKHYKIRNLDNGGFYISPRITFPGLHELVRHYTNASDGLCTRLSRPCQTQKPQKPWWEDEWEVPRETLKLVERLGAGQFGEVWMGYYNGHTKVAVKSLKQGSMSPDAFLAEANLMKQLQHQRLVRLYAVVTQEPIYIITEYMENGSLVDFLKTPSGIKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMVRPDNCPEELYQLMRLCWKERPEDRPTFDYLRSVLEDFFTATEGQYQPQP> SEQ ID NO: 40> VAV1 -MYO IF Fusion> Length: 952 amino acidsMELWRQCTHWLIQCRVLPPSHRVTWDGAQVCELAQALRDGVLLCQLLNNLLPHAIN LREVNLRPQMSQFLCLKNIRTFLSTCCEKFGLKRSELFEAFDLFDVQDFGKVIYTLSA LSWTPIAQNRGIMPFPTEEESVGDEDIYSGLSDQIDDTVEEDEDLYDCVENEEAEGDEI YEDLMRSEPVSMPPKMTEYDKRCCCLREIQQTEEKYTDTLGSIQQHFLKPLQRFLKP QDIEIIFINIEDLLRVHTHFLKEMKEALGTPGAANLYQVFIKYKERFLVYGRYCSQVES ASKHLDRVAAAREDVQMKLEECSQRANNGRFTLRDLLMVPMQRVLKYHLLLQELVI<HTQEAMEI<ENLRLALDAMRDLAQCVNEVI<RDNETLRQITNFQLSIENLDQSLAHY GRPKIDGELKITSVERRSKMDRYAFLLDKALLICKRRGDSYDLKDFVNLHSFQVRDD SSGDRDNKKWSHMFLLIEDQGAQGYELFFKTRELKKKWMEQFEMAISNIYPENATA NGHDFQMFSFEETTSCKACQMLLRGTFYQGYRCHRCRASAHKECLGRVPPCGRHGQ DFPGTMKKDKLHRRAQDKKRNELGLPKMEVFQEYYGLPPPPGAIGPFLRLNPGDIVE LTKAEAEQNWWEGRNTSTNEIGWFPCNRVKPYVHGPPQDLSVHLWYAGPMERAGA-99-4927-7786-8905.2Atty. Dkt. No.: 121384-0285ESILANRSDGTFLVRQRVKDAAEFAISIKYNVEVKHIKIMTAEGLYRITEKKAFRGLTE LVEFYQQNSLKDCFKSLDTTLQFPFKEPEKRTISRPAEPTRKGMAKGKPRRSSQAPTR AAPAPPRGMDRNGVPPSARGGPLPLEIMSGGGTHRPPRGPPSTSLGASRRPRARPPSE HNTEFLNVPDQGMAGMQRKRSVGQRPVPGVGRPKPQPRTHGPRCRALYQYVGQDV DELSFNVNEVIEILMEDPSGWWKGRLHGQEGLFPGNYVEKIEquivalents

[0223] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this technology belongs.

[0224] Although the foregoing refers to particular preferred embodiments, it will be understood that the present invention is not so limited. It will occur to those of ordinary skill in the art that various modifications may be made to the disclosed embodiments and that such modifications are intended to be within the scope of the present invention.

[0225] The present technology illustratively described herein may suitably be practiced in the absence of any element or elements, limitation or limitations, not specifically disclosed herein. Thus, for example, the terms “comprising,” “including,” “containing,” etc. shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the present technology claimed.

[0226] Thus, it should be understood that the materials, methods, and examples provided here are representative of preferred aspects, are exemplary, and are not intended as limitations on the scope of the present technology.

[0227] The present technology has been described broadly and generically herein. Each of the narrower species and sub-generic groupings falling within the generic disclosure also form part of the present technology. This includes the generic description of the present technology with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.-100-4927-7786-8905.2Atty. Dkt. No.: 121384-0285[02281 In addition, where features or aspects of the present technology are described in terms of Markush groups, those skilled in the art will recognize that the present technology is also thereby described in terms of any individual member or subgroup of members of the Markush group.10229] All publications, patent applications, patents, GenBank citations, ATCC citations, and other references mentioned herein are expressly incorporated by reference in their entirety, to the same extent as if each were incorporated by reference individually. In case of conflict, the specification, including definitions, will control.-101-4927-7786-8905.2

Claims

1. Atty. Dkt. No.: 121384-0285WHAT IS CLAIMED IS:

1. A vector comprising a nucleic acid sequence encoding a polypeptide, the polypeptide comprising at least one of: a) a T cell lymphoma wild-type protein or functional fragment thereof, or b) a T cell lymphoma mutant protein or functional fragment thereof, wherein the T cell lymphoma mutant protein or functional fragment thereof is a variant of the wild-type protein or functional fragment thereof.

2. The vector of claim 1, wherein the variant comprises a single-point, double-point, insertion, or fusion mutation of the wild-type protein.

3. The vector of claim 1 or 2, wherein the vector is selected from a plasmid, a herpes simplex virus, a retrovirus, an adenovirus, or an adeno-associated virus.

4. The vector of claim 3, wherein the retrovirus is a lentivirus.

5. The vector of any of claims 1-4, wherein the protein is selected from a variant or wild-type protein listed in in Tables 1 or 5.

6. The vector of any of claims 1-4, wherein the variant or wild-type protein is selected from a: FAS substitution at amino acid 265; FYN-TRAF3IP2 fusion; VAV1-STAP2 fusion; IL2RG substitution at amino acid 315; CTNNB1 substitution at amino acid 45; CAPRIN- JAK2 fusion; mCTLA4-mCD28 fusion; IKZF2-ERBB4 fusion; PABPC1-TYK2 fusion; IL7R mutation T244I245CPT; mCD3E substitution at amino acid 34; TRAF3 substitution at amino acid 359; IDH1 substitution at amino acid 132; AKT1 WT; IL2RG WT; TBL1XR1 WT; STAT3 substitution at amino acid 618; DNMT3A substitution at amino acid 882; IL7R substitution at amino acid 78; NFKB2 substitution at amino acid 882; RASGRP1 substitution at amino acid 261; AKT1 substitution at amino acid 17; MAPK1 substitution at amino acid 321; KHDRBS1-LCK fusion; VAV1-MY01F fusion; AKT1 wild-type; IL2RG wild-type; and / or TBL1XR1 WT.

7. The vector of any of claims 1-4, wherein the vector comprises a nucleic acid sequence comprising a sequence selected from SEQ ID NOs: 1-31.-102-4927-7786-8905.2Atty. Dkt. No.: 121384-02858. An engineered cell comprising the vector of any of claims 1-7.

9. An engineered cell comprising: a) at least one nucleic acid comprising a sequence selected from SEQ ID NOs: 1-31; or b) at least one polypeptide encoded by a sequence selected from SEQ ID NOs: 1-31.

10. The engineered cell of claim 8 or 9, wherein the engineered cell is a T cell.

11. The engineered cell of claim 10, wherein the T cell is selected from a CAR T cell, CD3+ cell, CD8+ cell, CD4+ cell, regulatory T cell, a gamma delta T cell (yST), an invariant natural killer T (iNKT) cell, a mucosal associated invariant T (MAIT) cell, a macrophage, a monocyte, a natural killer (NK) cell, a tumor infiltrating lymphocyte (TIL), a cytotoxic T cell, a T helper cell, a memory T cell, a central memory T (TCM) cell, a stem memory T (TSCM) cell, a stem-cell-like memory T cell (or stem-like memory T cells), an effector memory T (TEM) cell, a TEMRA (CD45RA+) cell, an effector T cell, a Thl cell, a Th2 cell, a Th9 cell, a Th 17 cell, a Th22 cell, a Tfh (follicular helper) cell, a natural killer T (NKT) cell, a transitional memory T (TTM) cell, a terminal effector T (TTE) cell, or a naive T (TN) cell.

12. The engineered cell of any of claims 8-11, wherein the T cell comprises a receptor with specificity for a target antigen.

13. The engineered cell of claim 12, wherein the target antigen is selected from CD19, B7H3 (CD276), BCMA (CD269), ALPPL2, Claudin 18.2, CD123, CD171, CD179a, CD20, CD213A2, CD22, CD24, CD246, CD272, CD30, CD33, CD38, CD44v6, CD46, CD71, CD97, CEA, Claudin 6(CLDN6), CLECL1, CS-1, DLL-3, EGFR, EGFRvIII, ELF2M, EpCAM, EphA2, Ephrin B2, FAP, FLT3, GCC, GD2, GD3, GM3, GPRC5D, HER2 (ERBB2 / neu), IGLL1, IL-llRa, KIT (CD 117), KLK2, LY6G6D, MUC1, NCAM, p53R175H, PAP, PDGFR-P, PRAME, PRSS21, PSCA, PSMA, ROR1, SIRPa, SSEA-4, TAG72, TEM1 / CD248, TEM7R, TSHR, VEGFR2, ALPI, citrullinated vimentin, cMet, and / or Axl.-103-4927-7786-8905.2Atty. Dkt. No.: 121384-028514. The engineered cell any of claims 8-13, wherein the target antigen is selected from cell surface receptors, adhesion proteins, integrins, mucins, lectins, tumor-associated antigens, and tumor-specific antigens.

15. The engineered cell of any of claims 8-14, wherein the engineered cell has increased or decreased signaling through the API, NF AT, NFKB, and / or PD1 pathways.

16. The engineered cell of any of claims 8-15, wherein the engineered cell has increased or decreased cytokine production.

17. The engineered cell of claim 16, wherein the cytokine is selected from IL-2, IL-4, II- 5, TNF alpha, IFN- gamma and / or IL-13.

18. A composition comprising the engineered cell of any of claims 8-17 and a pharmaceutically acceptable carrier.

19. A method to increase the persistence of T cells in a cancer cell, comprising contacting the tumor with the engineered cell of any of claims 8-17 or the composition of claim 18.

20. A method to increase the persistence of T cells in a tumor, comprising contacting the tumor with the engineered cell of any of claims 8-17 or the composition of claim 18.

21. The method of claim 20, wherein the contacting in in vivo or in vitro.

22. A method to increase the persistence of T cells in a tumor microenvironment or tumor draining lymph nodes of a subject in need thereof, comprising administering to the subject in the engineered cell of any of claims 8-17 or the composition of claim 18.

23. A method to prevent tumor recurrence in a subj ect in need thereof, comprising administering to the subject in need the engineered cell of any of claims 8-17 or the composition of claim 18 after a subject has reduced tumor growth or symptoms, optionally wherein the subject is in remission.

24. A method to inhibit the growth of a cancer and / or increase the survival rate of a subject, in need, comprising administering to the subject in with the engineered cell of any of claims 8-17 or the composition of claim 18.-104-4927-7786-8905.2Atty. Dkt. No.: 121384-028525. The method of any of claims 22-24, wherein the cancer is a small cell lung cancer, colorectal cancer, testicular cancer, ovarian cancer, melanoma, lymphoma, leukemia, multiple myeloma, prostate cancer, breast cancer, non-small cell lung cancer, gastric cancer, esophageal cancer, liver cancer, kidney cancer, head & neck cancer, glioblastoma, neuroblastoma, soft tissue sarcoma, uterine cancer, brain cancer, skin cancer, renal cancer, bladder cancer, pancreatic cancer, thyroid cancer, eye cancer, gastrointestinal cancer, carcinoma, or sarcoma.

26. The method of any of claims 22-24, wherein the cancer is a solid tumor.

27. A method to inhibit the growth of a first cancer and / or increase the survival rate of a subject in need, comprising administering to the subject in with the engineered cell of any of claims 8-17 or the composition of claim 18, wherein growth of a second cancer is also inhibited after the first tumor is contacted with the engineered cell or composition, and wherein the first cancer comprises an antigen recognized by the engineered cell.

28. The method of claim 27 wherein the first and the second cancer are the same or different.

29. The method of claim 27 or 28, wherein the second cancer is negative for the T-cell dependent antigen.

30. The method of any of claims 27-29, wherein the first cancer and / or second cancer is a small cell lung cancer, colorectal cancer, testicular cancer, ovarian cancer, melanoma, lymphoma, leukemia, multiple myeloma, prostate cancer, breast cancer, non-small cell lung cancer, gastric cancer, esophageal cancer, liver cancer, kidney cancer, head & neck cancer, glioblastoma, neuroblastoma, soft tissue sarcoma, uterine cancer, brain cancer, skin cancer, renal cancer, bladder cancer, pancreatic cancer, thyroid cancer, eye cancer, gastrointestinal cancer, carcinoma, or sarcoma.

31. The method of any of 27-29, wherein the first cancer is a tumor, and further optionally wherein the second cancer is a tumor.-105-4927-7786-8905.2Atty. Dkt. No.: 121384-028532. The method of any of claims 23-31, wherein the administration is parenteral (including intramuscular, subcutaneous, intradermal, intravascular, intravenous, intraarterial, intramedullary and intrathecal), intraperitoneal, or intratumoral.

33. The method of any of claims 23-31, wherein the subject in need is a mammal, optionally a human.

34. A method to generate a vector, comprising transferring a plasmid to a cell, wherein the plasmid comprises at least one of: a) a T cell lymphoma wild-type protein or functional fragment thereof, or b) a T cell lymphoma protein mutant or functional fragment thereof, wherein the T cell lymphoma protein mutant or functional fragment thereof is a variant of the wild-type protein or functional fragment thereof.

35. The method of claim 34, wherein the variant or wild-type protein is selected from a: FAS substitution at amino acid 265; FYN-TRAF3IP2 fusion; VAV1-STAP2 fusion; IL2RG substitution at amino acid 315; CTNNB1 substitution at amino acid 45; CAPRIN-JAK2 fusion; mCTLA4-mCD28 fusion; IKZF2-ERBB4 fusion; PABPC1-TYK2 fusion; IL7R mutation T244I245CPT; mCD3E substitution at amino acid 34; TRAF3 substitution at amino acid 359; IDH1 substitution at amino acid 132; AKT1 WT; IL2RG WT; TBL1XR1 WT; STAT3 substitution at amino acid 618; DNMT3A substitution at amino acid 882; IL7R substitution at amino acid 78; NFKB2 substitution at amino acid 882; RASGRP1 substitution at amino acid 261; AKT1 substitution at amino acid 17; MAPK1 substitution at amino acid 321; KHDRBS1-LCK fusion; VAV1-MY01F fusion; AKT1 wild-type; IL2RG wild-type; and / or TBL1XR1 WT.

36. The method of claim 34, wherein the nucleotide has a sequence according to at least one of SEQ ID NOs: 1-31.

37. The method of any of claims 34-36, wherein the vector is a retrovirus, optionally a lentivirus.-106-4927-7786-8905.2Atty. Dkt. No.: 121384-028538. A kit comprising optional instructions for use and one or more of the following: a vector of any one of claims 1-7, an engineered cell of any one of claims 8-17, or the composition of claim 19.-107-4927-7786-8905.2