The disclosure relates to antibodies that bind FcRn and methods of using these antibodies.

Provided are novel dipeptide repeat (DPR) specific antibodies (e.g., human-derived antibodies) as well as synthetic variants and biotechnological derivatives thereof, capable of binding C9orf72 poly-glycine-alanine DPRs, as well as methods and uses related thereto. The antibody of the present invention can be used in pharmaceutical and diagnostic compositions for DPR protein-targeted immunotherapy and diagnostics.

Disclosed are compounds represented by the following general formula (I): Cyclo-(Arg-Gly-Asp-X.sup.1-X.sup.2-X.sup.3-X.sup.4-X.sup.5) (I) wherein the variables groups X.sup.1 to X.sup.5 have the following meanings X.sup.1: Leu, Ile, Nle, Val, Tyr, Phe; X.sup.2: D-amino acid such as D-Pro, N-Me-D-Phe; X.sup.3: Pro, N-Me-amino acid such as N-Me-Lys, N-Me-Lys(Ac); Pro-Rx3, N-Me-Lys-Rx4; X.sup.4: Gly, Ala, Ser, Thr; X.sup.5: Leu, Ala, Tyr, His, Ile, Nle, Val, Phe wherein Pro-Rx3 represents a proline residue that carries at the C-3, C-4 or C-5 carbon atom and preferably the C-4 carbon atom a functional group selected from —NH2, —OH, —NH—Ac, —NH-hexyne, and wherein Lys-R.sup.x4 represents a lysine residue, wherein the ω-amino nitrogen atom carries a group of the formula -L4-R4, wherein L4 is selected from the group consisting of covalent bond, —C(O)—, and —C(O)—O—, . . . , and wherein R4 is selected from the group consisting of —(CH2)n-C≡CH with n=0, 1, 2, 3, 4, 5, 6, 7 or 8, or wherein the sub-sequence -X.sup.2-X.sup.3- represents a β-turn mimetic diffeωωring from the meanings above, or pharmaceutically acceptable salts, esters, solvates, polymorphs or modified forms thereof represented by the following general formula (II): (X.sup.0).sub.n1L(X.sup.8).sub.n2 wherein X0 represents the compound of the general formula (I) as specified above (excluding one hydrogen atom to allow bonding to the linker), L represents a linker, X.sup.8 represents the effector moiety and wherein n1 and n2 are each independently selected from the range of 1 to 5, preferably such that each of n1 and n2 represents 1, wherein n1+n2 represents the number of valencies of the linker and is preferably in the range of from 2 to 6, more preferably 2-5, with the proviso that each of n1 and n2 is at least 1, as well as uses therefore in therapy and imaging.

Radiation therapy or radiotherapy (RT) is a powerful treatment where precision and accuracy is crucial. Image Guided Radiotherapy (IGRT) facilitates more accurate position verification, correcting for anatomic changes related to internal organ movement. IGRT thereby helps reduce toxicity of radiotherapy and increases relapse-free survival. An inter-correlation point with a fixed position and volume (a marker) can be applied to indicate the point of treatment clearly in both imaging modalities and to localize and track tumors in real time. In this study, we present the development of a marker based on lactose octaacetate:octapropionate 1:1 containing 3 mM PLA-DTPA(Gd), 40% triglyceride, 5% propylene carbonate and 10% XSAIB (sucrose based CT-contrast agent). The injectable marker had high CT contrast (>1000 HU) and displayed clearly visible, stable T.sub.1 contrast enhancement (T.sub.1˜900 ms) in the rim over at least 3 weeks with clinically observable resolution.

A polypeptide conjugate for use in a method for binding and/or internalization of the polypeptide conjugate to a mammalian cell having a transferrin receptor (TFRC) and/or receptor for advanced glycation end products (RAGE). The polypeptide conjugate may be used in a method for targeting of a drug delivery system or diagnostic delivery system.

The present invention discloses indicator fluids, reference indicator fluid, and usage thereof, and systems and methods for assessing movement of molecular substances within, to or from a cerebrospinal fluid, brain or spinal cord compartment of a human cranio-spinal cavity. Indicator fluid moving from the cerebrospinal fluid compartment enables measurements of levels of indicator fluid in blood or urine and assessment of the cranio-spinal cavity's ability to remove molecular substances. The indicator fluids may be contrast agents used for imaging, such as by computed tomography imaging, and magnetic resonance imaging, or imaging utilizing radioactive substances by positron emission tomography, single-photon emission computed tomography or scintigraphy. Using these imaging modalities, the invention describes indicator fluids, systems and methods enabling assessment of movement of substances within, to or from a cerebrospinal fluid, brain or spinal cord compartment of a cranio-spinal cavity, and from the human cranio-spinal cavity to lymphatic pathways or kidneys.

Limit size lipid nanoparticles, methods for using the lipid nanoparticles, and methods and systems for making limit size lipid nanoparticles.

Low-molecular weight gadolinium (Gd)-based MR contrast agents for PSMA-specific T.sub.1-weighted MR imaging are disclosed. The (Gd)-based MR contrast agents exhibit high binding affinity for PSMA and exhibit specific T.sub.1 contrast enhancement at PSMA+ cells. The PSMA-targeted Gd-based MR contrast agents can be used for PSMA-targeted imaging in vivo. .sup.86Y-labeled PSMA-binding ureas also are provided, wherein the PSMA-binding ureas also are suitable for use with other radiotherapeutics.

The present disclosure relates to the generation of an antibody that specifically recognizes and binds Endosialin, a cell surface antigen characteristic of tumor pericytes and cells of tumor stroma. The antibody has the ability to become internalized in Endosialin expressing cells and to block the activation of MAPK in PDGF stimulated human pericytes. The antibody is able to block angiogenesis induced by LGALS3BP, a known Endosialin interactor and to inhibit tumor growth alone and in combination with 1959, a humanized antibody against LGALS3BP in human osteosarcoma xenograft. Furthermore, upon conjugation of the humanized version of the anti-Endosialin antibody with a duocarmycin derivative, the resulting ADC displays potent and antigen dependent in vitro tumor cell cytotoxicity and effective antitumor efficacy in vivo. The disclosure is also related to nucleotides encoding the antibodies of the disclosure and cell expressing the antibodies.

The present invention describes small molecule ligand-drug conjugates and methods of using the small molecule ligand-drug conjugates for targeted treatment of cancer in a patient in need thereof. Further described are methods of sterilizing circulating tumor cells and determining drug concentration in cancer tissue.