The present application relates to methods of treating and imaging cancer. The methods involve providing a first agent comprising a first targeting component coupled to a cancer therapeutic component or an imaging component and providing a second agent comprising a second targeting component alone, wherein the second targeting component increases the uptake, internalization, and/or retention of the first targeting component coupled to a cancer therapeutic component or imaging component. The first and second agents are then administered to a subject having cancer to treat cancer. Also disclosed is a combination therapeutic or a combination imaging system, each comprising the first and second agents.

The invention provides antigen binding domains that bind myeloid cell surface antigen CD33 protein comprising the antigen binding domains that bind CD33, polynucleotides encoding them, vectors, host cells, methods of making and using them.

The present invention relates in part to the discovery of genes that are deregulated in cancer stem cells (e.g., melanoma stem cells). In some aspects, methods for treating individuals having melanoma are provided; the methods involve modulating (e.g., inducing, inhibiting, etc.) the activity of the cancer stem cell associated genes. In other aspects, cell surface genes that are upregulated in melanoma stem cells are targeted for the selective isolation, detection, and killing of cancer stem cells in melanoma. Other aspects of the invention relate to reagents, arrays, compositions, and kits that are useful for diagnosing and treating melanoma.

The present technology provides compounds as well as compositions including such compounds useful for the treatment of cancers where the compounds are represented by the following formula

##STR00001##

or a pharmaceutically acceptable salt thereof, wherein M is an alpha-emitting radionuclide.

The present invention relates to a method for generating an antibody-payload conjugate by means of a microbial transglutaminase (MTG). The method comprises a step of conjugating a linker comprising or having the structure (shown in N—>C direction) Aax-(Sp.sub.1)-B.sub.1-(Sp.sub.2) via a primary amine in the N-terminal residue Aax to a glutamine (Gln) residue comprised in the heavy or light chain of an antibody, wherein Aax is an amino acid having the structure NH.sub.2—Y—COOH, wherein Y comprises a substituted or unsubstituted alkyl or heteroalkyl chain; (Sp.sub.1) is a chemical spacer or is absent; (Sp.sub.2) is a chemical spacer or is absent; and B.sub.1 is a linking moiety or a payload. Further the present invention relates to antibody-linker conjugates that have been generated with the method of the invention and uses thereof.

Provided herein are methods, kits, and compositions for stratifying and treating subjects, e.g., subjects having cancer. In some examples, the methods involve use of a radiolabelled heavy chain variable domain derived from a heavy chain antibody (V.sub.HH), or a functional fragment thereof, as both a screening agent and a treatment agent. In some examples, the V.sub.HH, or a functional fragment thereof, that is radiolabelled with a radioisotope that is both a γ-emitter and β-emitter.

A targeted radiopharmaceutical of chemical Formula I, below, is disclosed wherein Q.sup.+3 is a

##STR00001## trivalent radioactive isotope ion; M is a proton (H+), an ammonium ion or an alkali metal ion; “g” is a number that is 1 to about 12; the boxed mAb MNPR-101 represents the chemically-bonded humanized mAb MNPR-101; and Y− is an optional anion present in an amount needed to balance the ionic charge. A pharmaceutical composition that comprises a theranostic effective amount of a Formula I targeted radiopharmaceutical dissolved or dispersed in a pharmaceutically acceptable diluent is also disclosed, as are a method for treating and/or diagnosing a mammalian host having a disease, disorder or condition characterized by undesired angiogenesis, tumor growth and/or tumor metastasis. A targeted pro-radiopharmaceutical construct similar to that of Formula I but without the radioisotope (Formula III) is also contemplated.

This invention provides a method for treating a subject afflicted with cancer, comprising administering to the subject (i) a BCL-2 inhibitor in conjunction with (ii) an alpha-emitting isotope-labeled agent that targets cancer cells in the subject, wherein the amounts of the BCL-2 inhibitor and labeled agent, when administered in conjunction with one another, are therapeutically effective. This invention also provides a method for inducing the death of a cancer cell, comprising contacting the cell with (i) a BCL-2 inhibitor in conjunction with (ii) an alpha-emitting isotope-labeled agent that targets the cancer cell, wherein the amounts of BCL-2 inhibitor and labeled agent, when concurrently contacted with the cell, are effective to induce the cell's death.

The present invention relates to conjugates including a chelating moiety of a metal complex thereof and a therapeutic or targeting moiety, methods for their production, and uses thereof.

Combination therapies comprising administering radioimmunoconjugates and one or more checkpoint inhibitors.