Abstract: Combination therapies for the treatment of cancers are provided. In some embodiments, a flagellin derivative such as CBLB502 is administered in combination with an immune checkpoint therapy (e.g., an anti-PD 1 antibody and an anti-CTLA4 antibody) to treat a cancer in a mammalian subject. In some embodiments, the combination therapy is administered intratumorally or peritumorally.

Abstract: Provided herein are agents, such as antibodies, antibody-drug conjugates, or chimeric antigen receptors, that target B7-H3. Methods of treating cancer are provided, comprising administering to a patient in need thereof an effective amount of an B7-H3-targeting agent. The patient may be selected for treatment if the cancer expresses an increased level of B7-H3.

Abstract: The present disclosure provides radiolabeled compounds of the formula: (I) and (II), as well as precursor compounds of the formula: (VII) wherein the variables are defined herein. The present disclosure also provides radiopharmaceutical compositions comprising the radiolabeled compounds disclosed herein as well as precursor compositions comprising the precursor compounds disclosed herein. The present disclosure further provides methods of imaging using the radiolabeled compounds and/or radiopharmaceutical compositions of the present disclosure as well as kits for the preparation of the radiolabeled compounds and radiopharmaceutical compositions disclosed herein.

Abstract: Tracers that can be used for PET or SPECT imaging of the distribution of Pgp are disclosed. The tracers are metalloprobes that can comprise a radioactive metal ion such as 67Ga or 68Ga. Methods of synthesizing the tracers, and methods of imaging heart and other tissues are also disclosed. The tracers can be used to obtain high signal-to-background ratios for imaging tissues in vivo such as heart or tumor tissue. In various embodiments, disclosed tracers can exhibit, a) enhanced first pass extraction into heart tissue compared to presently available probes, b) linearity with true blood flow, c) enhanced detection of myocardial viability compared to presently available probes, d) reduced liver retention compared to presently available probes, and e) more efficient clearance from non-cardiac and adjoining tissues compared to presently available probes.

Abstract: Zaprinast has been discovered to have activity against glutaminase 1, an important metabolic enzyme in selected cancers, for example, glutamine-dependent cancer types. Thus, glutamine-dependent cancer types, such as IDH1/2 gain-of-function mutant cancers or GLI1 overexpressing cancers, may be particularly sensitive to Zaprinast analogues.

Abstract: Tracers that can be used for PET or SPECT imaging of the distribution of Pgp are disclosed. The tracers are metalloprobes that can comprise a radioactive metal ion such as 67Ga or 68Ga. Methods of synthesizing the tracers, and methods of imaging heart and other tissues are also disclosed. The tracers can be used to obtain high signal-to-background ratios for imaging tissues in vivo such as heart or tumor tissue. In various embodiments, disclosed tracers can exhibit, a) enhanced first pass extraction into heart tissue compared to presently available probes, b) linearity with true blood flow, c) enhanced detection of myocardial viability compared to presently available probes, d) reduced liver retention compared to presently available probes, and e) more efficient clearance from non-cardiac and adjoining tissues compared to presently available probes.

Abstract: Methods of imaging distribution of myeloperoxidase activity in a subject are disclosed. These methods include the use of bioluminescent substrates, including luminol and wavelength-shifted analogues of luminol. Bioluminescent myeloperoxidase substrates that emit light at longer wavelengths compared to luminol are shown to be useful for imaging myeloperoxidase activity in vivo. The disclosed methods can be used for imaging sites of inflammation and other pathological conditions associated with abnormal levels of MPO activity in vivo. Methods of synthesis of luminol analogues are also disclosed.

Abstract: Methods and compositions for treating sepsis using cell membrane-permeant peptide conjugate covalent compounds having target cell specificity are provided.

Abstract: Methods of imaging distribution of myeloperoxidase activity in a subject are disclosed. These methods include the use of bioluminescent substrates, including luminol and wavelength-shifted analogues of luminol. Bioluminescent myeloperoxidase substrates that emit light at longer wavelengths compared to luminol are shown to be useful for imaging myeloperoxidase activity in vivo. The disclosed methods can be used for imaging sites of inflammation and other pathological conditions associated with abnormal levels of MPO activity in vivo. Methods of synthesis of luminol analogues are also disclosed.

Abstract: Novel blood-brain barrier permeant amyloid-targeting peptides and peptide conjugates are described. The peptide conjugates include a radioisotope or other label in a stable complex that translocates across brain capillary endothelial cell monolayers. The labeled peptide conjugate binds to amyloid plaques (A?) associated with Alzheimer's disease, and is useful for the targeted delivery of therapeutic and diagnostic molecules into the brain.

Abstract: Methods and compositions for treating sepsis and diseases and conditions involving cellular apoptosis using cell membrane-permeant peptide conjugates of a cell membrane permeant peptide together with anti-apoptotic domains of the TCL1 protein are provided.

Abstract: The invention provides methods of delaying the onset, slowing the progression, preventing, or treating Alzheimers disease in a subject. In particular, the invention provides methods of modulating transport of A? across the blood brain barrier of the subject.

Abstract: Methods of treatment of sepsis are disclosed. These methods comprise administering to a subject a composition comprising at least one siRNA directed against at least one gene encoding a pro-apoptotic polypeptide. The pro-apoptotic polypeptide, in some aspects, can be other than Fas or caspase-8. In some embodiments, an siRNA can be directed against a pro-apoptotic component of the mitochondrial pathway, such as a pro-apoptotic bcl-2 protein. In some aspects, an siRNA can be directed against a BH3-only bcl-2 protein, while in other aspects, siRNAs can be directed against multi BH domain Bcl-2 family members such as bax and bak. In some embodiments, an siRNA can be directed against a death receptor pathway molecule such as FADD. In various configurations, a composition can also comprise a cationic lipid such as DOTAP, or nanoparticles comprising a cyclodextrin-containing polycation and a polymer such as a poly(ethylene glycol).

Abstract: An enhanced firefly luciferase protein fragment complementation assay method is described that produces a robust and broadly applicable bioluminescence signal and demonstrates both modification-independent and phosphorylation-dependent protein interactions in intact living human cells and animals useful as a diagnostic and testing tool in living biologic systems in research and in assays.

Abstract: The present invention provides heterologous complementation systems and methods of using the systems to detect molecular interactions. In particular, the heterologous complementation systems comprise polypeptide fragments derived from heterologous polypeptides. If a molecular interaction occurs, then the heterologous polypeptide fragments are able to associate and produce a detectable signal.

Abstract: Methods and compositions for medical imaging, evaluating intracellular processes and components, radiotherapy of intracellular targets, and drug delivery by the use of novel cell membrane-permeant peptide conjugate coordination and covalent complexes having target cell specificity are provided. Kits for conjugating radionuclides and other metals to peptide coordination complexes are also provided.

Abstract: Methods and compositions for medical imaging, evaluating intracellular processes and components, radiotherapy of intracellular targets, and drug delivery by the use of novel cell membrane-permeant peptide conjugate coordination and covalent complexes having target cell specificity are provided. Kits for conjugating radionuclides and other metals to peptide coordination complexes are also provided.

Abstract: Methods and compositions for treating sepsis and diseases and conditions involving cellular apoptosis using cell membrane-permeant peptide conjugates of a cell membrane permeant peptide together with anti-apoptotic domains of the TCL1 protein are provided.

Abstract: Methods and compositions for treating sepsis using cell membrane-permeant peptide conjugate covalent compounds having target cell specificity are provided.

Abstract: Novel blood-brain barrier permeant amyloid-targeting peptides and peptide conjugates are described. The peptide conjugates include a radioisotope or other label in a stable complex that translocates across brain capillary endothelial cell monolayers. The labeled peptide conjugate binds to amyloid plaques (A?) associated with Alzheimer's disease, and is useful for the targeted delivery of therapeutic and diagnostic molecules into the brain.