Abstract: Provided herein is a one-step method for chelating actinium-225 to a construct comprising a chelator linked to a biomolecule, such as, an antibody or monoclonal antibody, via a bifunctional ligand in, for example, a 3-arm configuration. Also provided are methods for increasing the radiochemical yield of an actinium-225-chelant-biomolecule complex and for producing a high specific activity actinium-225 complex. The chelation is performed at a physiological temperature, about 37° C. Also provided are high specific activity actinium-225 complexes, that is, actinium-225 chelated to the chelator-biomolecule construct and pharmaceutical compositions thereof. Further provided are methods of treating a neoplastic disease or disorder with the actinium-225 complexes.

Abstract: The present invention provides a method for predicting the treatment response of a human bladder cancer patient, the method comprising: a) measuring the gene expression of at least 9, at least 10, at least 15, at least 20 or at least 30 of the genes from Group 1 in Table 10 and at least 1, at least 2, at least 3 or at least 5 of the genes from Groups 2-4 in Table 10 in a sample obtained from the bladder tumour of the patient to obtain a sample gene expression profile of at least said genes; and b) making a prediction of the treatment response and/or prognosis of the patient based on the sample gene expression profile. Related methods and systems are also described. The invention finds particular use in predicting whether a bladder cancer patient is likely to be sensitive to (chemo)radiation therapy.

Abstract: The presently disclosed subject matter provides chimeric antigen receptors (CARs) that specifically target CD19 and cells comprising such CD19-targeted CARs. The presently disclosed subject matter further provides uses of the CD19-targeted CARs for treatment, e.g., for treating blood cancer.

Abstract: The present invention provides a method for predicting the treatment response of a human gastroesophageal cancer patient, the method comprising: a) measuring the gene expression of at least 3 of the following genes: CDH1, CDK6, COX2, ELOVL5, GATA4, EGFR, TBCEL, FGF7, CDH17, FNBP1, PIP5K1B, TWIST, CD44, MET, CEACAM1, TOX3, GLIPR2, GSTP1, RON, TMEM136, MYB, BRCA2, FGF1, POU5F1, EPR, DPYD, ABL2 and SH3RF1 in a sample obtained from the gastroesophageal tumour of the patient to obtain a sample gene expression profile of at least said genes; and b) making a prediction of the treatment response and/or prognosis of the patient based on the sample gene expression profile. Also provided are related computer-implemented methods and methods of treatment of gastroesophageal cancer.

Abstract: The present invention provides a compound having the structure: or a pharmaceutically acceptable salt or ester thereof, and a method of treating a subject afflicted with pain, a depressive disorder, a mood disorder or an anxiety disorder by administering the compound to the subject.

Abstract: A method for characterising motion of one or more objects in a time ordered image dataset comprising a plurality of time ordered data frames, the method comprising: selecting a reference data frame from the plurality of time ordered data frames (210); extracting a plurality of image patches from at least a part of the reference data frame (220); identifying a location of each image patch of at least a subset of the plurality of image patches in each data frame (230); defining, based on the identified locations, a mesh for each data frame, wherein vertices of each mesh correspond to respective identified locations of image patches in the corresponding data frame (240); and deriving, from the meshes, a motion signature for the time ordered image dataset, the motion signature characteristic of the motion of the one or more objects in the plurality of time ordered data frames (250).

Abstract: The present invention relates to methods of designing kinase mutants for reprogramming the sensitivity of a target kinase to some specific inhibitors, methods of reprogramming the sensitivity of a target kinase to some specific inhibitors, wherein those kinase inhibitors have little or no affinity for the wild-type target kinase, vectors or cells expressing said mutated kinases, composition and uses thereof for the prevention and/or treatment of a disease or disorder, in particular cancer.

Abstract: The present invention relates to methods for the joint analysis of regulation of gene expression and gene expression in single cells. Provided are methods for obtaining gene expression information for a single nucleus, the methods comprising deriving a DNA library from the genomic DNA in one or more nuclei and deriving an RNA library from the RNA in one or more nuclei, sequencing the molecules in the RNA library and the DNA library, and correlating the RNA library and the DNA library for each of the one or more nuclei.

Abstract: The present disclosure provides hCG variant proteins, nucleic acid molecules encoding the same, vectors comprising nucleic acid molecules, compositions comprising the same, and methods of treating cancer.

Abstract: The present invention provides an anti-cancer vaccine comprising: (i) at least one peptide comprising the amino acid sequence of a neoantigen encoded by a mutant homologous recombination (HR) DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D, wherein the mutant gene comprises a reversion mutation; and/or (ii) at least one polynucleotide encoding the at least one peptide of (i). Also provided are engineered T cells that recognise said neoantigen. Related methods and medical uses of the vaccine and/or engineered T cell are provided, including for the treatment of cancers, such as homologous recombination (HR) deficient cancers that acquire PARP inhibitor resistance or platinum resistance by development of reversion mutations in an HR DNA repair gene selected from the group: BRCA1, BRCA2, PALB2, CDK12, RAD51B, RAD51C and RAD51D.

Abstract: The invention provides compounds, methods, pharmaceutical compositions, and kits for the treatment of proliferative disorders such as cancer. In one aspect, the methods comprise compounds that inhibit the activity of protein kinases, such as cell division cycle (Cdc) kinase. In another aspect, the methods comprise compounds that inhibit Cdc7 and/or Dbf4 activity. In another aspect, the methods comprise compounds that exhibit anti-proliferative properties useful in treating diseases such as cancer. Compounds useful for any of the methods include compounds of the Formula (A) or (B): or pharmaceutically acceptable salts thereof. Exemplary compounds of Formula (A) or (B) include granaticin A, granaticin B, dihydrogranaticin A, dihydrogranaticin B, medermycin, and actinorhodin.

Abstract: The invention relates to chimeric antigen receptors (CARs) targeting a cancer-associated antigen and their use for treatment of a tumor or cancer. In particular, the invention provides compositions and methods for treating diseases associated with the antigen NGcGM3. The invention also relates to CARs specific to NGcGM3, vectors encoding the same, and recombinant T cells comprising the CARs 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 NGcGM3.

Abstract: The instant disclosure provides antibodies that specifically bind to CTLA-4 (e.g., human CTLA-4) and antagonize CTLA-4 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.

Abstract: Provided herein, inter alia, are compounds and methods for inhibiting PLK4 and for treating cancer in a subject in need thereof.

Abstract: Provided are compounds of the Formula (I), or a pharmaceutically acceptable salt thereof: wherein W, X, Y, Z, x, R1, R2, R3, x and n are defined in the specification. The compounds are inhibitors of lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) family members (LOXL1, LOXL2, LOXL3, LOXL4) and are useful in therapy, particularly in the treatment of cancer. Also disclosed are LOX inhibitors for use in the treatment of a cancer associated with EGFR and biomarkers that predict responsiveness to a LOX inhibitor.

Abstract: This invention concerns various methods of using labeled HSP90 inhibitors to improve treatment of cancer patients with HSP90 inhibitors, including ex vivo and in vivo methods for determining whether a tumor will likely respond to therapy with an HSP90 inhibitor.

Abstract: An x-ray micro-beam radiation production system is provided having: a source of accelerated electrons, an electron focusing component configured to focus the electrons provided by the source, and a target which produces x-rays when electrons impinge thereon from the source. The electron focusing component is configured to focus the electrons provided by the source such that they impinge at a focal spot having a width ? formed on a surface of the target.

Abstract: The present disclosure provides novel dominant negative Fas polypeptides comprising a first modification in the cytoplasmic domain and a second modification in the N-terminal region of human Fas. The present disclosure also provides cells comprising such novel dominant negative Fas polypeptides and an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR) or a T cell receptor (TCR)). Also provided are uses of the cells for treatment, e.g., for treating tumors and pathogen infections.

Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a mutant Epidermal Growth Factor Receptor (EGFR), and methods of using the dsRNA to inhibit expression of mutant EGFR.

Abstract: The present disclosure is directed, in part, to methods and systems of intra-operatively identifying a retained surgical item by imaging a surgical item with an intra-operative imaging device to obtain image data, imaging a patient suspected of having a retained surgical item with an intra-operative imaging device to obtain image data, interacting the image data to a module configured to identify the surgical item from the intra-operative surgical item image data, and identifying the retained surgical item from the surgical item image data.