The present invention relates to methods and kits or articles of manufacture related thereto that may find use, inter alia, in assessing responsiveness of cancers to MUC16 antagonists by monitoring HE4 expression. In some embodiments, the methods include measuring the level of expression of HE4 in a sample from a subject; comparing the level of expression of HE4 in the sample with the level of expression of HE4 in a sample previously obtained from the subject; and, optionally, administering to the subject a therapeutically effective amount of a MUC16 antagonist.

It is intended to provide an antitumor drug having an excellent therapeutic effect, which is excellent in terms of antitumor effect and safety. There is provided an antibody-drug conjugate in which an antitumor compound represented by the following formula is conjugated to an anti-TROP2 antibody via a linker having a structure represented by the following formula: -L.sup.1-L.sup.2-L.sup.P-NH—(CH.sub.2)n.sup.1-L.sup.a-(CH.sub.2)n.sup.2-C(═O)— wherein the anti-TROP2 antibody is connected to the terminal of L.sup.1, and the antitumor compound is connected to the carbonyl group of the —(CH.sub.2)n.sup.2-C(═O)— moiety with the nitrogen atom of the amino group at position 1 as a connecting position.

Provided are isolated nucleic acid molecules encoding chimeric antigen receptors (CARs) that bind to tumor antigens. Also provided are isolated polypeptides and CARs encoded by the isolated nucleic acid molecules, vectors that include the isolated nucleic acid molecules, cells that include the isolated nucleic acid molecules, methods of making the same, and methods for using the same to generate a persisting population of genetically engineered T cells in a subject, expanding a population of genetically engineered T cells in a subject, modulating the amount of cytokine secreted by a T cell, reducing the amount of activation-induced calcium influx into a T cell, providing an anti-tumor immunity to a subject, treating a mammal having a MUC1-associated disease or disorder, stimulating a T cell-mediated immune response to a target cell population or tissue in a subject, and imaging a MUC1-associated tumor.

In various embodiments the invention provides anti-mucin-like protein (MLP) monoclonal antibodies, compositions and methods for detecting MLP as a biomarker for mucin-secreting type of cancer such as ovarian or pancreatic cancer.

Compositions and methods for targeted delivery of active agents to cells are provided. The compositions comprise a wholly or partially double-stranded synthetic DNA carrier, and an active agent intercalated in double-stranded portions of the DNA carrier. The DNA carrier may also be linked to a targeting agent. The compositions are useful for delivering an active agent into a targeted cell type, for example a cytotoxic agent.

The present invention relates to therapeutic ADCs comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment, more particularly sacituzumab govitecan. The ADC is administered to a subject with a Trop-2 positive cancer that is resistant to or relapsed from prior treatment with a checkpoint inhibitor. The therapy is effective to treat cancers that are resistant to checkpoint inhibitors.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to Trop-2 or CEACAM5 and the immunoconjugate may be administered at a dosage of between 4 mg/kg and 16 mg/kg, preferably 4, 6, 8, 9, 10, 12, or 16 mg/kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Surprisingly, the immunoconjugate is effective to treat cancers that are refractory to or relapsed from irinotecan.

Described herein are compositions and methods of use of anti-Trop-2 antibodies or antigen-binding fragment thereof to isolate, enrich, detect, diagnose and/or characterize circulating tumor cells (CTCs) from patients with a Trop-2 positive cancer. Preferably, the antibody is an RS7, 162-46.2 or MAB650 antibody. The compositions and methods are of use to detect, diagnose and/or treat metastatic Trop-2.sup.+ cancers, such as breast, ovarian, cervical, endometrial, lung, prostate, colon, rectum, stomach, esophageal, bladder, renal, pancreatic, thyroid, epithelial or head-and-neck cancer.

Cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate are disclosed are all embodiments of the invention. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CA6 glycotope. The present invention is also directed to humanized or resurfaced versions of DS6, an anti-CA6 murine monoclonal antibody, and epitope-binding fragments thereof.

The invention provides an agent for preventing or treating a condition characterised by the presence of unwanted cells, the agent comprising: (i) a targeting moiety that is capable of targeting to the unwanted cells; and (ii) a T cell antigen, wherein the T cell antigen can be released from the targeting moiety by selective cleavage of a cleavage site in the agent in the vicinity of the unwanted cells.