The present disclosure provides KMT2A-MAML2 fusion nucleic acid molecules, and KMT2A-MAML2 fusion polypeptides, as well as methods, kits and reagents for detecting such KMT2A-MAML2 fusion nucleic acid molecules and KMT2A-MAML2 fusion polypeptides. The disclosure also provides methods for evaluating, identifying, assessing, and/or treating an individual having a cancer, such an epithelial neoplasm or a thymoma.

In some aspects, the disclosure provides antibody-based reagents that specifically bind a tropomyosin receptor kinase B (TrkB) isoform that is associated with cancers. In some embodiments, the isoform is TrkB.T1. In some embodiments, the antibody or antibody derivative specifically binds a polypeptide comprising, consisting essentially of, or consisting of the sequence FVLFHKIPLDG (SEQ ID NO:1), or a sequence with at least 80% sequence identity thereto. In other aspects, the disclosure provides methods of producing the antibody or antibody derivative, related hybridomas, and methods of detecting and treating cancers incorporating use of the disclosed antibody reagents.

The present invention is based in part on the identification of biomarkers, including NQO1, NRF2 and KEAP1, predictive of cancer cell responsiveness to treatment with ML 329 or a derivative thereof.

The present invention is based in part on the identification of biomarkers, including NQO1, NRF2 and KEAP1, predictive of cancer cell responsiveness to treatment with ML 329 or a derivative thereof.

The present teachings relate generally to conjugates and methods for imaging a tumor microenvironment in a patient, and to conjugates and methods for imaging cancer-associated fibroblasts (CAFs) in the tumor microenvironment of a patient. The present teachings relate generally to method of making conjugates comprising a fibroblast activation protein (FAP) inhibitor.

The field of this invention relates to immunohistochemistry (IHC) and in situ hybridization (ISH) for the targeted detection and mapping of biomolecules (e.g., proteins and miRNAs) in tissues or cells for example, for research use and for clinical use such by pathologists (e.g., biomarker analyses of a resected tumor or tumor biopsy). In particular, the use of mass spectrometric imaging (MSI) as a mode to detect and map the biomolecules in tissues or cells for example. More specifically, the field of this invention relates to photocleavable mass-tag reagents which are attached to probes such as antibodies and nucleic acids and used to achieve multiplex immunohistochemistry and in situ hybridization, with MSI as the mode of detection/readout. Probe types other than antibodies and nucleic acids are also covered in the field of invention, including but not limited to carbohydrate-binding proteins (e.g., lectins), receptors and ligands. Finally, the field of the invention also encompasses multi-omic MSI procedures, where MSI of photocleavable mass-tag probes is combined with other modes of MSI, such as direct label-free MSI of endogenous biomolecules from the biospecimen (e.g., tissue), whereby said biomolecules can be intact or digested (e.g., chemically digested or by enzyme).

It relates to immune cells (e.g., T cells such as CAR-T cells, NK cells such as CAR-NK cells) modified to have no or reduced expression and/or function of one or more target proteins selected from the group consisting of: Signal Peptide Peptidase Like 3 (SPPL3), FADD, FAS, CASP8, ARID1A, BAK1, BID, ETS1, IKZF2, and HIST1H1B (such as SPPL3), uses thereof, and methods for generating thereof. Also provided are uses of the one or more target proteins (e.g., SPPL3) as a biomarker.

An image analysis method for determining the biomedical state of a tissue sample. The method includes receiving a digital image of a tissue sample, identifying the number and location of A-type cells and B-type cells, obtaining an observed relative distribution, obtaining a reference relative distribution of expected distances between reference A-type cells and reference B-type cells, computing a proximity score as a difference of the reference relative distribution and the observed relative distribution, computing a combined score comprising the proximity score and the density of the A-type cells and/or the density of the B-type cells, and using the combined score for determining the biomedical state of the tissue sample and/or outputting the combined score.

An image analysis method for determining the biomedical state of a tissue sample. The method includes receiving a digital image of a tissue sample, identifying the number and location of A-type cells and B-type cells, obtaining an observed relative distribution, obtaining a reference relative distribution of expected distances between reference A-type cells and reference B-type cells, computing a proximity score as a difference of the reference relative distribution and the observed relative distribution, computing a combined score comprising the proximity score and the density of the A-type cells and/or the density of the B-type cells, and using the combined score for determining the biomedical state of the tissue sample and/or outputting the combined score.

Antibodies that bind to AXL protein and variants thereof are described herein. AXL exhibits a distinct and limited expression pattern in normal adult tissue(s), and is aberrantly expressed in the cancers listed in Table I. Consequently, the MAbs of the invention provide a diagnostic composition for the treatment and management of cancer.