The present disclosure provides binding agents, such as antibodies, that specifically bind Angiopoietin-like protein 8 (ANGPTL8), including human ANGPTL8, and methods of their use.

A method of generating corrected fluorescence data of concentrations of a targeted fluorophore in tissue of a subject includes administering first and second fluorescent contrast agents to the subject, the first contrast agent targeted to tissue of interest, the second agent untargeted. The tissue is illuminated with light of a first stimulus wavelength and first data is acquired at an appropriate emissions wavelength; the tissue is illuminated at a second stimulus wavelength and second data is acquired at a second emissions wavelength associated with the second agent, the first and second emissions wavelength differ. Difference data is generated by subtracting the second data from the first data. A system provides for stimulus and capture at multiple wavelengths, with image storage memory and subtraction code, to perform the method. Corrected data may form an fluorescence image, or is used to generate fluorescence tomographic images.

Described herein are therapeutic pH responsive compositions comprising a block copolymer and a therapeutic agent useful for the treatment of cancer.

Peptides that home, target, migrate to, are directed to, are retained by, or accumulate in and/or bind to the cartilage or kidney of a subject are disclosed. Pharmaceutical compositions and uses for peptides or peptide-active agent complexes comprising such peptides are also disclosed. Such compositions can be formulated for targeted delivery of an active agent to a target region, tissue, structure or cell in the cartilage. Targeted compositions of the disclosure can deliver peptide or peptide-active agent complexes to target regions, tissues, structures, or cells targeted by the peptide.

Described herein are protein-payload conjugates and compositions thereof that are useful, for example, for target-specific delivery of therapeutic and/or imaging agent moieties. In certain embodiments, provided are specific and efficient methods for producing protein-payload constructs (e.g., antibody-drug conjugates) utilizing a combination of transglutaminase and Diels-Alder techniques. Antibody-drug conjugates and compositions which comprise glutaminyl-modified antibodies, Diels-Alder adducts, and reactive payloads and are provided.

Provided herein are agents, such as antibodies, antibody-drug conjugates, or chimeric antigen receptors, that target B7-H3. Methods of treating cancer are provided, comprising administering to a patient in need thereof an effective amount of an B7-H3-targeting agent. The patient may be selected for treatment if the cancer expresses an increased level of B7-H3.

There are provided a compound of Formula (1) and a labeled biological substance having the compound.

##STR00001##

Z.sup.1 and Z.sup.2 represent a specific 6-membered ring. However, at least one of Z.sup.1 or Z.sup.2 is a benzene ring having a specific substituent at an ortho position with respect to a nitrogen atom to which L.sup.1 or L.sup.2 is bonded, or a specific nitrogen-containing 6-membered ring in which a ring-constituting atom located at the ortho position is a nitrogen atom.

R.sup.1 to R.sup.4, R.sup.11 to R.sup.13, L.sup.1, L.sup.2, and R.sup.21 represents specific groups, and n, α1, α2, and m represent specific numbers.

The compound has at least one structure represented by —(CH.sub.2—CH.sub.2—O).sub.m-R.sup.21 on a heterocyclic ring and has at least one substituent capable of being bonded to a carboxy group or a biological substance at a specific position, and in a case where at least one of Z.sup.1 or Z.sup.2 is the specific nitrogen-containing 6-membered ring, the specific substituents may be bonded to each other to form a ring.

The near-infrared window of fluorescent heptamethine cyanine dyes greatly facilitates biological imaging because there is deep penetration of the light and negligible background fluorescence. But dye instability, aggregation, and poor pharmacokinetics are current drawbacks that limit performance and the scope of possible applications. All these limitations are simultaneously overcome with a new molecular design strategy that produces a charge balanced and sterically shielded fluorochrome. The key design feature is a meso-Aryl group that simultaneously projects two shielding arms directly over each face of a linear heptamethine polyene. Cell and mouse imaging experiments compared a shielded heptamethine cyanine dye (and several peptide and antibody bioconjugates) to benchmark heptamethine dyes and found that the shielded systems possess an unsurpassed combination of photophysical, physiochemical and biodistribution properties that greatly enhance bioimaging performance.

The invention relates generally to polypeptides that include at least a first cleavable moiety (CM1) that is a substrate for at least one matrix metalloprotease (MMP) and at least a second cleavable moiety (CM2) that is a substrate for at least one serine protease (SP), to activatable antibodies and other larger molecules that include these polypeptides that include at least a CM1 that is a substrate for at least one MMP protease and at least a CM2 that is a substrate for at least one SP protease, and to methods of making and using these polypeptides that include at least a CM1 that is a substrate for at least one MMP protease and at least a CM2 that is a substrate for at least one SP protease in a variety of therapeutic, diagnostic and prophylactic indications.

Methods for evaluating micrometastases in a tissue region of a subject are described. The methods include administering to the subject a detectably effective amount of a tumor-targeted photoactivatable immunoconjugate; allowing a sufficient amount of time for the tumor-targeted photoactivatable immunoconjugate to enter micrometastases in the tissue region; illuminating the tumor-targeted photoactivatable immunoconjugate; obtaining an image of the tissue region of the subject using a fluorescent imaging device, and evaluating the micrometastases in the tissue region by conducting algorithmic analysis of the image. Methods of treating micrometastases in a tissue region of a subject are also described.