Presented herein are cancer peptide agents and uses thereof for treating cancer and/or inhibiting metastasis. Also presented herein are methods of treating cancer, or inhibiting metastasis of cancer in a subject, comprising administering a therapeutically effective amount of a composition comprising one or more cancer peptide agents to the subject. Also presented herein is a method of treating a cancer in a subject, or inhibiting metastasis of a cancer in a subject that comprises administering a therapeutically effective amount of a composition comprising one or more cancer peptide agents, and administering a chemotherapy or chemotherapeutic agent.

Described herein are mutations that confer resistance to treatment with a BTK inhibitor. Described herein are modified BTK polypeptides that exhibit decreased inhibition (i.e. are resistant) to a covalent and/or irreversible BTK inhibitor. Also described herein modifications of PLCy2 and CARD 11 polypeptides that confer resistance to treatment with a BTK inhibitor. Described herein are diagnostic methods for detecting the modified polypeptides and nucleic acids encoding the modified polypeptides and applications of the methods thereof. Described herein are compositions, combinations, and kits containing the modified polypeptides and methods of using the modified polypeptides. Also described herein are methods of using modified BTK polypeptides as screening agents for the identification and design of second-generation BTK inhibitors.

The invention disclosed herein is based on the identification of novel mutations in the JAK2 gene and JAK2 protein. The invention provides compositions and methods useful for diagnosing hematopoietic diseases including, for example, myeloproliferative diseases. The invention also provides compositions and methods useful for determining a prognosis of an individual diagnosed as having a hematopoietic disease.

The disclosure provides compositions and methods for inducing programmed cell death, such as necroptosis. Compositions may comprise fusion proteins comprising a death inducing domain and a multimerization domain; nucleic acids encoding fusion proteins; and cells comprising fusion proteins. The compositions may be used in methods such as cancer therapy, including in combination with additional immunotherapeutics.

The present disclosure provides methods and compositions for prognosing Chronic Lymphocytic Leukemia (CLL) or monitoring CLL therapy in a subject, by contacting a blood sample from a subject having CLL with one or more tyrosine phosphorylation (pTyr) probes to promote binding of tyrosine phosphorylated proteins in the blood sample to the one or more pTyr probes to generate pTyr probe-protein complexes; and detecting an amount of pTyr probe-protein complexes in the blood sample; wherein an amount of pTyr probe-protein complexes in the blood sample is compared to a control to indicate expected progression of CLL, or therapeutic efficacy of CLL therapy in the subject.

The present invention provides methods for inhibiting Fyn kinase, using 5-3-pyridin-2-amine, 6-3-imidazo[1,2-a] pyrazine, 6-3-imidazo[1,2-b] pyridazine, N-(5-imidazo [2,1-b][1,3,4] thiadiazol-2-yl)-amine, 4-3-1H-pyrazolo[3,4-b] pyridine, and N-(3-imidazo [1,2-b] pyridazin-6-yl) amine compounds and methods of treatment, prevention, inhibition or amelioration of diseases and conditions associated with Fyn kinase using such compounds.

The present disclosure relates to a method of identifying an agent-of-interest that alters binding or activity of a client protein to a chaperone, co-chaperone, or chaperone-co-chaperone complex, the method including: determining a three-dimensional (3D) structure of a client protein-of-interest; evaluating the 3D structure of the client protein-of-interest to identify an unstable substructure of the 3D structure of the client protein-of-interest; and determining an amino acid sequence of the unstable substructure of the 3D structure of the client protein-of-interest to identify an agent-of-interest that alters binding or activity of a client protein to a chaperone, co-chaperone, or chaperone-co-chaperone complex.

Chimeric receptors featuring major histocompatibility molecules grafted onto T cell receptor molecules and surrogate co-receptors featuring cell surface receptor ligands fused with signaling molecule domains. The chimeric receptors can be used to redirect cells, altering their specificity. T cells expressing chimeric receptors may bind to ICRs of target T cells for which their chimeric receptors are specific. Surrogate co-receptors may be used to help enhance TCR-CD3 signaling as part of this modular receptor system. The chimeric receptors and surrogate coreceptors may be used to help eliminate autoreactive T cells or program T cells to desired effector functions.

The present invention relates to a polypeptide binding to fibroblast growth factor receptor 3 isoforms 3b and 3c (FGFR3b and FGFR3c), wherein the polypeptide comprises an amino acid sequence selected from the group consisting of: (a) GVTLFVALYDYEVYGPTPMLSFHKGEKFQIL(X.sup.1)(X.sup.2)(X.sup.3) (X.sup.4)GPYWEARSL(X.sup.5)TGETG(X.sup.6)IPSNYVAPVDSIQ (SEQ ID NO: 1), wherein amino acid positions (X1) to (X.sup.6) may be any amino acid sequence; (b) an amino acid sequence which is at least 95% identical to the amino acid sequence of (a), wherein the identity determination excludes amino acid positions (X.sup.1) to (X.sup.6) and provided that the amino acid sequence EVYGPTPM (SEQ ID NO: 2) in amino acid positions 12 to 19 of SEQ ID NO: 1 is conserved and the amino acids P and Y in amino acid positions 37 and 38 of SEQ ID NO: 1 are conserved; (c) GVTLFVALYDYEVMSTTALSFHKGEKF QILSQSPHGQYWEARSLTTGETG(X.sup.6)IPSNYVAPVDSIQ (SEQ ID NO: 19), wherein the amino acid position (X.sup.6) may be any amino acid; and (d) an amino acid sequence which is at least 95% identical to the amino acid sequence of (c), wherein the identity determination excludes amino acid position (X.sup.6) and provided that the amino acid sequences EVMSTTA (SEQ ID NO: 20) in amino acid positions 12 to 18 of SEQ ID NO: 19 and SQSPH (SEQ ID NO: 21) in amino acid positions 31 to 35 of SEQ ID NO: 19 are conserved and the amino acids Q and Yin amino acid positions 37 and 38 of SEQ ID NO: 19 are conserved.

Described herein are compositions and methods for treating, inhibiting or ameliorating X linked agammaglobulinemia (XLA) in subjects that have been identified or selected as being ones that would benefit from a therapy to treat, inhibit, or ameliorate XLA. Exemplary embodiments include constructs and methods for gene therapy, which restore or increase BTK expression.