This disclosure describes the characteristics of the “energetic” cancer stem cell (e-CSC) phenotype. This distinct sub-population of cancer stem cells (CSCs) has a unique energetic profile compared to bulk CSCs, being more glycolitic, having higher mitochondrial mass and elevated oxidative metabolism. e-CSCs also show an increased capacity to undergo cell cycle progression, enhanced anchorage-independent growth, and ALDH-positivity. The e-CSC phenotype presents new targets for cancer therapeutics, and in particular the anti-oxidant response, mitochondrial energy production, and mitochondrial biogenesis of e-CSCs makes them highly susceptible to mitochondrial inhibitors that target e-CSC anti-oxidant response, mitochondrial energy production, and mitochondrial biogenesis. Gene products for e-CSCs are disclosed, as well as classes of mitochondrial inhibiting therapeutic agents. Also disclosed are methods for identifying and separating e-CSCs front bulk cell populations.

The present invention is directed to a method for diagnosis or prognosis of a disease in a subject and/or predicting a risk of getting a disease or adverse event in a subject and/or monitoring a disease or adverse event in a subject by determining the level of peptidylglycine alpha-amidating monooxygenase (PAM) and/or its isoforms and/or fragments thereof in a sample of bodily fluid of said subject.

Disclosed are surprising new methods and kits for treating patients, particularly cancer patients, using bavituximab in combination therapies with immuno-oncology (IO) agents such as checkpoint inhibitor antibodies. The methods and kits are based on the surprising finding that human patients treated with bavituximab and checkpoint inhibitor antibodies have a statistically significant prolonged survival in controlled studies.

An assay measuring protease mediated degradation of type IV collagen and its biomarker potential for identifying cancer patients with a T-cell permissive tumor microenvironment is described.

Methods of treating patients diagnosed with AML or MDS harboring mutant IDH-1 include detecting an IDH1 mutation and the therapeutic administration of an inhibitor of a mutant IDH-1 as a single agent, or in combination with azacitidine (AZA) or cytarabine.

Methods of diagnosing and predicting cancer relapse comprising measuring soluble CD28 levels in a subject, wherein an increase in soluble CD28 is indicative of cancer relapse or imminent cancer relapse, are provided. Methods of determining response to PD-1/PD-L1 based immunotherapy in a subject in need thereof, comprising measuring sCD28 levels in a subject undergoing PD-1/PD-L1 based immunotherapy at at least two time points wherein a decrease indicates response and an increase indicates lack of response, are also provided.

Specific binding members, particularly antibodies and fragments thereof, which bind to transforming growth factor beta 3 (TGF-β3) are provided, particularly recognizing human and mouse TGF-β3, particularly antibodies and fragments that do not recognize or bind TGF-β1 or TGF-β2. Particular antibodies are provided which specifically recognize and neutralize TGF-β3. These antibodies are useful in the diagnosis and treatment of conditions associated with activated or elevated TGF-β3, including cancer, and for modulating immune cells and immune response, including immune response to cancer or cancer antigens. The anti-TGF-β3 antibodies, variable regions or CDR domain sequences thereof, and fragments thereof may also be used in therapy in combination with chemotherapeutics, immune modulators, or anti-cancer agents and/or with other antibodies or fragments thereof. Antibodies of this type are exemplified by the novel antibodies hereof, including antibody MTGF-β3-9, MTGF-β3-12, MTGF-β3-16, MTGF-β3-17 and MTGF-β3-19, whose sequences are provided herein.

Disclosed herein are compositions comprising a CT20 peptide and methods of using the disclosed compositions to treat cancers expressing chaperonin containing TCP (CCT).

The present invention relates to extracellular microvesicles biomarkers for determining the tumour transformation status or presence of a tumour in a subject, and to the uses of such biomarkers and to diagnostics methods using such biomarkers. In particular, the methods and uses of the invention involve isolation of TM9SF4-positive extracellular vesicles and detection of the expression of a second biomarker, preferably selected from the group consisting of CD9 protein, miR-21 and RNU6.

Provided herein are compositions and methods for identifying cancer cells. In particular, provided herein are optimized assays for identifying a variety of different cancer cells present in a sample at low concentrations.