Provided herein is technology relating to predicting a subject's resistance or responsiveness to a decitabine based therapy and particularly, but not exclusively, to methods, compositions, and related uses for predicting a subject's resistance or responsiveness to a decitabine based therapy wherein the subject is diagnosed with chronic myelomonocytic leukemia.

The present invention provides an approach for the determination of the activation states of a plurality of proteins in single cells. This approach permits the rapid detection of heterogeneity in a complex cell population based on activation states, expression markers and other criteria, and the identification of cellular subsets that exhibit correlated changes in activation within the cell population. Moreover, this approach allows the correlation of cellular activities or properties. In addition, the use of modulators of cellular activation allows for characterization of pathways and cell populations.

Described herein are novel anti-PD1 antibody reagents (e.g., antibodies, antigen-binding fragments thereof, and/or chimeric antigen receptors). Also described herein antibody-drug conjugates or kits comprising the disclosed antibody reagents, as well as methods of treating cancer by administering the disclosed antibody reagents.

The present invention provides: a method for identifying a blood cancer patient who may benefit from a monotherapy using a drug comprising a DNA methyl transferase inhibitor and a combination therapy using the aforesaid drug together with another epigenetic controller; a pharmaceutical composition to be used in treating a patient who has been identified or selected by the method; and a kit for identifying such a patient. More particularly, the aforesaid method comprises a step for measuring the expression amount of DUSP5 in a sample obtained from a blood cancer patient. When the expression amount measured in this step is lower than a reference expression amount of DUSP5, then the patient is identified or selected as a blood cancer patient who may benefit from a treatment using the drug comprising a DNA methyl transferase inhibitor.

The invention relates to peripheral blood mononuclear cell (PBMC) monolayers or bone-marrow cell monolayers and methods for its culture and corresponding uses of said monolayers. The present invention also relates, in some aspects, to screening methods comprising the PBMC monolayer or bone-marrow cell monolayer of the invention for determination of response or lack of response of a disease to a therapeutic agent and/or drug screening methods. In some aspects, the invention further relates to methods for diagnosing a disease or predisposition to a disease in a PBMC donor or bone-marrow cell donor comprising the PBMCs/bone-marrow cells cultured according to the method of the invention and/or to methods for determining whether the disease is likely to respond or is responsive to treatment with a therapeutic agent.

The invention provides, inter alia, methods of prognosing the survival of a multiple myeloma patient based levels of TP53RK in multiple myeloma cells of the patient. Also provided are methods of screening for therapeutic agents for treating multiple myeloma based on their ability to decrease TP53RK levels or activity in a patient with multiple myeloma.

The present invention relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TCR beta constant region 1 (TRBC1) or TRBC2; cells; such a T cells comprising such a CAR; and the use of such cells for the treatment of a T-cell lymphoma or leukaemia in a subject.

The present invention relates to medical imaging, disease monitoring and theranostic approaches in neoplastic diseases of certain anti-CD38 single-domain antibodies (sdAb).

Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to CD38, are capable of killing CD38.sup.30 cells by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and/or complement-dependent cytotoxicity (CDC). Said antibodies and fragments thereof may be used in the treatment of tumors that express CD38 protein, such as multiple myeloma, chronic lymphocytic leukemia, chronic rnyelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia, or the treatment of autoimmune and inflammatory diseases such as systemic lupus, rheumatoid arthritis, multiple sclerosis, erythematosus, and asthma. Said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of CD38, Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CD38 protein.

The present invention is based in part on the identification of DPH1 and other members of the diphthamide synthesis pathway as biomarkers of resistance to an ADP-ribosylating toxin in a cell, and methods for identification, assessment, and treatment of a condition that is resistant to an ADP-ribosylating toxin.