The present invention provides cell-targeting molecules which can deliver a CD8+ T-cell epitope cargo to the MHC class I presentation pathway of a target cell. The cell-targeting molecules of the invention can be used to deliver virtually any CD8+ T-cell epitope from an extracellular space to the MHC class I pathway of a target cell, which may be a malignant cell and/or non-immune cell. The target cell can then display on a cell-surface the delivered CD8+ T-cell epitope complexed with MHC I molecule. The cell-targeting molecules of the invention have uses which include the targeted labeling and/or killing of specific cell-types within a mixture of cell-types, including within a chordate, as well as the stimulation of beneficial immune responses. The cell-targeting molecules of the invention have uses, e.g., in the treatment of a variety of diseases, disorders, and conditions, including cancers, tumors, growth abnormalities, immune disorders, and microbial infections.

Described herein is the use of rabbit hybridoma technology, along with a panel of truncated mesothelin domain fragments, to identify anti-mesothelin mAbs that bind specific regions of mesothelin. In one aspect of the present disclosure, the rabbit mAbs bind an epitope that is not part of Region I. In particular, the identified mAbs (YP187, YP223, YP218 and YP3) bind either Region II (391-486), Region III (487-581) or a native conformation of mesothelin with subnanomolar affinity. These antibodies do not compete for binding with the mesothelin-specific immunotoxin SS1P or mesothelin-specific antibody MORAb-009. In another aspect, disclosed is a high-affinity rabbit mAb that binds Region I of mesothelin (YP158). YP158 binds native mesothelin protein in cancer cells and tissues with high affinity and specificity.

Provided is a monoclonal antibody which specifically recognizes B cell lymphoma cells and a use thereof. More specifically, provided are the monoclonal antibody; a pharmaceutical composition for preventing or treating B cell lymphoma including the monoclonal antibody; a composition for diagnosing B cell lymphoma including the monoclonal antibody; a method for providing information for diagnosing B cell lymphoma using the monoclonal antibody; a chimeric antigen receptor (CAR) protein including i) the antibody, ii) a transmembrane domain, and iii) an intracellular signaling domain; a recombinant vector which expresses the CAR protein; a CAR-modified T cell transformed with the recombinant vector; a pharmaceutical composition for preventing or treating B cell lymphoma including the CAR-modified T cell; and an antibody-drug conjugate wherein the monoclonal antibody and a drug are conjugated.

Disclosed herein are recombinant adenoviruses with one or more nucleotide sequences inserted between two viral transcription units, formulations comprising the recombinant adenoviruses, and methods of treatment using the recombinant adenoviruses. In some embodiments, the one or more nucleotide sequences are inserted in an IX-E2 insertion site and/or an L5-E4 insertion site.

The present invention relates to anti-HER2 binding molecules (e.g., antibodies and antigen binding fragments thereof), derived HER2-binding molecules (e.g., bispecific anti-HER2 antibodies), and antibody-drug conjugates (ADC) that bind the extracellular domain of the HER2 receptor. Also provided are pharmaceutical formulation comprising the disclosed compositions and method for the treating diseases associated with HER2-mediated signal transduction.

The disclosure provides a force-dependent drug release system. The system is configured such that the drug is only released and subsequently internalized by cancer cells, which exert at least a threshold amount of force on a DNA component of the system. The system includes a tension sensor that is used to release a chemotherapeutic agent selectively into cancer cells. The system includes a first nucleic acid single strand of DNA or DNA analog that is conjugated to a substrate, and a second nucleic acid single strand of DNA or DNA analog that is hybridized to the first single strand. The second single strand is conjugated to a cytotoxic molecule that includes a cell surface receptor ligand and a chemotherapeutic agent. The second single strand is not conjugated to the substrate. Also provided are cancer cells that display a surface receptor ligand that is bound to the cytotoxic molecule. Also provided are one or more cancer cells that have internalized a single strand conjugated to the cytotoxic molecule, but have not internalized the first strand. Also provided are methods of treating cancer by administering the system The disclosure also provides a method for treating cancer by administering to an individual in need thereof. Also provided is a method for screening or testing chemotherapeutic agents for use in the system.

Provided herein are trioxacarcin-antibody drug conjugates of Formula (A): and pharmaceutically acceptable salts thereof, comprising at least one instance of the group -L.sup.1-(A-L.sup.2)a-B attached thereto, wherein a is an integer between 1 and 10, inclusive, L.sup.1 is absent or is a linking group, A is a moiety formed from the reaction of two complimentary groups (X and Y), L.sup.2 is absent or is another linking group, and B is an antibody or antibody fragment. Also provided are methods of preparing these antibody-drug conjugates, pharmaceutically acceptable compositions thereof, and methods of their use and treatment. Further provided are precursors to the trioxacarcin-antibody drug conjugates, novel trioxacarcins without an antibody conjugated thereto, pharmaceutical compositions thereof, and methods of their use and treatment. ##STR00001##

The present invention relates to a CD43 epitope expressed on human acute leukemia and lymphoblastic lymphoma cells and its use. More particularly, the present invention relates to a CD43 epitope expressed on human acute leukemia, lymphoblastic lymphoma cells, but not on mature hematopoietic cells, hematopoietic stem cells and non-hematopoietic cells, and to its diagnostic and therapeutic application on acute leukemia and lymphoblastic lymphoma.

The identification of Her2-specific monoclonal antibody m860 is described. The m860 antibody was identified from a human naïve phage display Fab library by panning against the extracellular domain of human Her2. M860 binds to cell surface-associated Her2 with an affinity comparable to that of trastuzumab (Herceptin®), but binds to a different epitope. Using site-specific glycan engineering, m860 was conjugated to the small molecule drug auristatin F. The antibody-drug conjugate was stable, bound cell-surface expressed Her2 and exhibited potent cell killing of Her2-positive cancer cells, including trastuzumab-resistant breast cancer cells.

The invention relates to HER3/HER2 bispecific antibodies binding to the beta-hairpin of HER3 and domain II of HER2, their preparation and use as medicament.