It is an object of the present invention to provide a medicament for killing tumor cells, having few side effects. According to the present invention, provided is a medicament for killing tumor cells that express a target substance at a low level on the cell surface thereof, said medicament comprising: a conjugate of a substance that binds to a target substance on the surface of tumor cells and a cytotoxin; and a photosensitizing dye.

The present invention provides p97-antibody conjugates and related compositions and methods, which may be used in any of a variety of therapeutic methods, including methods for the treatment of cancers such as Her2/neu-expressing and Her1/EGFR-expressing cancers.

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.

There is disclosed derivatives of amanitin conjugated to a targeting antibody to form an ADC (antibody drug conjugate).

The invention relates to a therapeutic combination for use as a medicament, wherein the therapeutic combination comprises: (a) a first pharmaceutical composition comprising a first proteinaceous molecule and at least one saponin covalently bound to said first proteinaceous molecule; and (b) a second pharmaceutical composition comprising a second proteinaceous molecule, comprising an effector moiety, wherein the binding site of the first proteinaceous molecule and the binding site of the second proteinaceous molecule are the same. The invention also relates to the first pharmaceutical composition for use as a medicament. The invention also relates to the first pharmaceutical composition, further comprising the second proteinaceous molecule. The invention also relates to the first pharmaceutical composition, further comprising the second proteinaceous molecule, for use as a medicament. Furthermore, the invention relates to the first pharmaceutical composition, further comprising the second proteinaceous molecule, for use in the treatment or prophylaxis of cancer in a patient in need thereof.

The invention provides an immunoconjugate of formula:

##STR00001##

or pharmaceutically acceptable salt thereof, wherein subscript r is an integer from 1 to 10, subscript n is an integer from about 2 to about 25, and “Ab” is an antibody construct that has an antigen binding domain that binds HER2. The invention further provides compositions comprising and methods of treating cancer with the immunoconjugate.

The present invention provides Ligand-Drug Conjugates and Drug-Linker Compounds comprising a methylene carbamate unit. The invention provides inter alia, Ligand-Drug Conjugates, wherein the Ligand-Drug Conjugate is comprised of a Self-immolative Assembly Unit having a methylene carbamate unit for conjugation of a drug to a targeting ligand, methods of preparing and using them, and intermediates thereof. The Ligand-Drug Conjugates of the present invention are stable in circulation, yet capable of inflicting cell death once free drug is released from a Conjugate in the vicinity or within tumor cells.

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 invention relates to a therapeutic combination, comprising a first proteinaceous molecule comprising a first binding site for binding to a first epitope of a first cell-surface molecule, the first proteinaceous molecule provided with at least one saponin covalently bound to an amino-acid residue of said first proteinaceous molecule, and comprising a second pharmaceutical composition comprising a second proteinaceous molecule different from the first proteinaceous molecule, the second proteinaceous molecule comprising a second binding site for binding to a second epitope of a second cell-surface molecule different from the first cell-surface molecule, and comprising an effector moiety, wherein the second epitope is different from the first epitope. An aspect of the invention is a composition comprising the first proteinaceous molecule and the second proteinaceous molecule of the invention. The invention also relates to an antibody-drug conjugate comprising the first proteinaceous molecule of the invention and an effector moiety. An aspect of the invention relates to a pharmaceutical composition comprising the composition or the antibody-drug conjugate of the invention, and optionally further comprising a pharmaceutically acceptable excipient. The invention also relates to the therapeutic combination or the composition or the antibody-drug conjugate or the pharmaceutical composition of the invention, for use as a medicament. The invention also relates to the therapeutic combination of the invention for use in the treatment or prophylaxis of a cancer.

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.