The invention relates to a sensor molecule for detecting a target molecule comprising: (a) a rod-like molecule L and a rod-like molecule R connected to each other by a joint molecule C to form a hinge; (b) a target binding molecule A bonded to the end of rod-like molecule L opposite to the joint molecule C; (c) a binding molecule A′ bonded to the end of rod-like molecule R opposite the joint molecule C; wherein the target binding molecule A is arranged to bind to the target molecule to be detected, and binding molecule A′ is arranged to bind to: i) the same target molecule as target binding molecule A; or ii) a complex of the target binding molecule A and the target; and wherein the hinge is biased into an open position, such that target binding molecule A and binding molecule A′ are biased apart by the hinge.

The invention features compositions and methods for treating and preventing cancer. In one aspect, isolated fusion proteins are provided that comprise a DNAJBI portion and a PRKACA portion. In a further aspect, compositions are provided, including immunogenic compositions that comprise an isolated fusion protein comprising a DNAJBI portion and a PRKACA portion. In a yet further aspect, a cancer vaccine is provided that comprises an isolated fusion protein comprising a DNAJBI portion and a PRKACA portion.

Certain embodiments of the invention provide a method of detecting the presence of a biomarker associated with resistance to an mTOR kinase inhibitor in a subject, comprising determining the presence of the biomarker in a physiological sample from the subject, wherein the sample comprises a nucleic acid.

A vector harboring nucleic acids encoding a recombinant T cell receptor having antigenic specificity for a DnaJ heat shock protein family member B1-protein kinase cAMP-activated catalytic subunit alpha (DNAJB1-PRKACA) fusion protein is provided, as are host cells and a method for treating fibrolamellar hepatocellular carcinoma with the vector.

The present disclosure relates to a modified peptide including (i) an amino acid sequence (X)-GRT-(Y)-TLC-(Z), or (ii) an amino acid sequence having at least 40% sequence identity to the amino acid sequence (X)-GRT-(Y)-TLC-(Z), wherein X, Y, and Z are the same as described in the specification. In this regard, methods for inhibiting the activity of at least one enzyme selected from the group consisting of AKT1 (PKB alpha), AKT2 (PKB beta), MAP3K8 (COT), MST4, AURKB (Aurora B), ROCK1, RPS6KB1 (p70S6K), CDC42 BPA (MRCKA), BRAF, RAF1 (cRAF) Y340D Y341D, SGK (SGK1), MAP4K4 (HGK), AURKA (Aurora A), AURKC (Aurora C), BRAF V599E, CHEK1 (CHK1), GSG2 (Haspin), CHEK2 (CHK2), FGR, IKBKB (IKK beta), CDK7/cyclin H/MNAT1, and CDC42 BPB (MRCKB) and Abl; and inhibiting cell proliferation are also provided, as are methods for preventing or treating cancer or a neurodegenerative disease or disorder.

The invention provides compositions and methods for treating diseases associated with expression of a cancer associated antigen as described herein. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen and modified T-cell receptor (TCR) T cells as described herein, vectors encoding the same, and recombinant T cells comprising the CARs or TCRs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen as described herein. In one aspect, the invention includes a composition comprising a nucleic acid sequence encoding a T cell signaling molecule and a nucleic acid sequence encoding a peptide comprising an amphipathic helix domain and a cluster of basic amino acids, wherein the peptide disrupts protein kinase A and an A-kinase anchoring protein (AKAP) association. The invention also includes a peptide that disrupts the PKA and AKAP association, such as through binding the RI subunit of the PKA with high affinity, thus preventing PKA from anchoring to the cell membrane.

Disclosed herein are switchable chimeric receptors, switchable chimeric receptor effector cells and chimeric receptor effector cell switches. The switchable chimeric receptor-ECs are generally T cells. The chimeric receptors have non-antibody extracellular domains that recognize a chimeric receptor binding partner on the chimeric receptor-EC switch or target cell. The chimeric receptor-ECs and switches may be used for the treatment of a disease or condition in a subject in need thereof.

It has been found that canine ECPKA protein secrets in a high level and an autoantibody against the canine ECPKA protein is formed in dogs with cancer. It is also found that human ECPKA does not selectively bind to a canine ECPKA autoantibody and cannot serve as a biomarker. In addition, canine ECPKA autoantibody detection can be used as a meaningful diagnosis tool for cancer in dogs only when quantitative measurement of such antibodies is adapted. When the measurement of canine ECPKA autoantibody is not conclusive, measuring CRP can provide supplemental data that can be used to improve the predictability of the canine ECPKA autoantibody measurement.

Certain embodiments of the invention provide a method of detecting the presence of a biomarker associated with resistance to an mTOR kinase inhibitor in a subject, comprising determining the presence of the biomarker in a physiological sample from the subject, wherein the sample comprises a nucleic acid.

The present disclosure relates to a modified peptide including (i) an amino acid sequence (X)-GRT-(Y)-TLC-(Z), or (ii) an amino acid sequence having at least 40% sequence identity to the amino acid sequence (X)-GRT-(Y)-TLC-(Z), wherein X, Y, and Z are the same as described in the specification. In this regard, methods for inhibiting the activity of at least one enzyme selected from the group consisting of AKT1 (PKB alpha), AKT2 (PKB beta), MAP3K8 (COT), MST4, AURKB (Aurora B), ROCK1, RPS6KB1 (p70S6K), CDC42 BPA (MRCKA), BRAF, RAFI (cRAF) Y340D Y341D, SGK (SGK1), MAP4K4 (HGK), AURKA (Aurora A), AURKC (Aurora C), BRAF V599E, CHEK1 (CHK1), GSG2 (Haspin), CHEK2 (CHK2), FGR, IKBKB (IKK beta), CDK7/cyclin H/MNAT1, and CDC42 BPB (MRCKB) and Ab!; and inhibiting cell proliferation are also provided, as are methods for preventing or treating cancer or a neurodegenerative disease or disorder.