Disclosed are methods relating to the use of circular PCMTD1 as a diagnostic and prognostic marker for leukemias and cancers with a p53 mutation and/or BCR/ABL fusions. Additionally, disclosed herein are oligonucleotides and antibodies that can be used to identify the circular PCMTD1 for use in the diagnostic and prognostic methods and target the circular PCMTD1 in treatment methods.

Disclosed are methods relating to the use of circular PCMTD1 as a diagnostic and prognostic marker for leukemias and cancers with a p53 mutation and/or BCR/ABL fusions. Additionally, disclosed herein are oligonucleotides and antibodies that can be used to identify the circular PCMTD1 for use in the diagnostic and prognostic methods and target the circular PCMTD1 in treatment methods.

The present application relates to antibodies which bind specifically to chelated radionuclides, including bispecific antibodies. It further relates to the use of such bispecific antibodies in applications such as radioimmunoimaging and radioimmunotherapy. It additionally relates to clearing agents and compositions useful in such methods. The chelated radionuclides may be a DOTAM-lead (Pb) chelate.

The present application relates to antibodies which bind specifically to chelated radionuclides, including bispecific antibodies. It further relates to the use of such bispecific antibodies in applications such as radioimmunoimaging and radioimmunotherapy. It additionally relates to clearing agents and compositions useful in such methods. The chelated radionuclides may be a DOTAM-lead (Pb) chelate.

The present invention discloses that cancer cells secrete succinate into extracellular milieu, which increases macrophage migration and mediates TAM polarization. Furthermore, succinate induces cancer cell EMT, enhances cancer cell migration, and promotes cancer metastasis in murine models. It is indicated in the present invention that serum succinate concentration is elevated in patients with lung cancer when compared to healthy subjects. It implies that during cancer development and progression, cancer cells release a large quantity of succinate into the circulation. As shown in the present invention, serum succinate has a high discriminatory power, it represents a new class of circulating oncometabolite with potential value for predicting NSCLC. Furthermore, as elevation of succinate level in LLC tumor model is accompanied by increased TAMs in the subcutaneous tumors and enhanced cancer metastasis, serum succinate may be a useful therapeutic biomarker for NSCLC treatment. The present invention also provides an anti-succinate antibody that can serve as a cancer therapeutic agent.

The present invention discloses that cancer cells secrete succinate into extracellular milieu, which increases macrophage migration and mediates TAM polarization. Furthermore, succinate induces cancer cell EMT, enhances cancer cell migration, and promotes cancer metastasis in murine models. It is indicated in the present invention that serum succinate concentration is elevated in patients with lung cancer when compared to healthy subjects. It implies that during cancer development and progression, cancer cells release a large quantity of succinate into the circulation. As shown in the present invention, serum succinate has a high discriminatory power, it represents a new class of circulating oncometabolite with potential value for predicting NSCLC. Furthermore, as elevation of succinate level in LLC tumor model is accompanied by increased TAMs in the subcutaneous tumors and enhanced cancer metastasis, serum succinate may be a useful therapeutic biomarker for NSCLC treatment. The present invention also provides an anti-succinate antibody that can serve as a cancer therapeutic agent.

A method of treating or preventing the onset of diabetes or diabetic complications comprises administering to a subject a composition comprising an anti-AGE antibody. A composition for treating or preventing the onset of diabetes or diabetic complications comprises a first anti-AGE antibody, a second anti-AGE antibody and a pharmaceutically acceptable carrier. The first anti-AGE antibody is different from the second anti-AGE antibody. A method of treating or preventing the onset of diabetes or diabetic complications comprises immunizing a subject in need thereof against AGE-modified proteins or peptides of a cell.

The present invention relates to the field of single-domain antibodies (sdAb) directed towards the glycans of the globo series, and in particular Globo H. More in detail, the present invention relates to sdAbs specifically binding one or more glycans selected from Globo H, Gb3, Gb4, and Gb5. The invention also provides polypeptides comprising multimeric single domain antibodies, as well as T cell chimeric antigen receptors comprising said anti-glycan sdAbs. Thus, the present invention provides polypeptides that can be used for targeting and/or treating several types of cancers associated with cells over-expressing said Globo H and/or Gb3, Gb4, Gb5. The present invention also relates to recombinant nucleic acid sequences encoding said polypeptides, and expression vectors and host cells comprising the same.

The present invention relates to the field of single-domain antibodies (sdAb) directed towards the glycans of the globo series, and in particular Globo H. More in detail, the present invention relates to sdAbs specifically binding one or more glycans selected from Globo H, Gb3, Gb4, and Gb5. The invention also provides polypeptides comprising multimeric single domain antibodies, as well as T cell chimeric antigen receptors comprising said anti-glycan sdAbs. Thus, the present invention provides polypeptides that can be used for targeting and/or treating several types of cancers associated with cells over-expressing said Globo H and/or Gb3, Gb4, Gb5. The present invention also relates to recombinant nucleic acid sequences encoding said polypeptides, and expression vectors and host cells comprising the same.

The present invention relates to the field of structural biology. More specifically, the present invention relates to an antigen-binding chimeric protein, called a MegaBody™, specifically binding a nanodisc, more specifically a membrane-scaffold protein (MSP)n which may be part of the nanodisc. The invention further provides for methods and uses of said nanodisc-specific antigen-binding chimeric proteins in three-dimensional high-resolution structural analysis of membrane proteins assembled within nanodiscs. The MSP-binding MegaBodies of the invention provide for a generic tool in membrane protein structural biology, more particular in Cryo-EM, by reducing preferred particle orientation of nanodiscs and of the entrapped target membrane proteins.