Disclosed herein are double payload antibody-drug conjugates (ADCs) and compositions comprising ADCs and one or more pharmaceutically acceptable carriers. Also, disclosed herein are methods for using these ADCs and compositions comprising ADCs and one or more pharmaceutically acceptable carriers to treat various cancers. Also disclosed herein are kits comprising compositions comprising ADCs.

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof pharmaceutical compositions containing them, and to their use in therapy for the prevention treatment of 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 EGP-1 (TROP-2), CEACAM5, CEACAM6, CD74, CD19, CD20, CD22, CSAp, HLA-DR, AFP or MUC5ac and the immunoconjugate may be administered at a dosage of between 4 mg/kg and 24 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 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.

The present disclosure provides, inter alia, multi-drug Antibody Drug Conjugates (MD-ADCs) and Linking Assembly (LA) Units, that are constructed in a site-specific matter via ‘orthogonal’ deprotection and drug loading. Also provided are, Protected Linking Assembly Units, which allow for ‘orthogonal’ deprotection and construction of MD-ADCs and LA Units of the present disclosure.

Provided is a separated antigen binding protein, containing at least one CDR in VH with the amino acid sequence as shown in SEQ ID NO: 1 or SEQ ID NO: 46; and at least one CDR in VL with the amino acid sequence as shown in SEQ ID NO: 2. Also provided are an immunoconjugate containing the separated antigen binding protein, nucleic acid coding the separated antigen binding protein, a carrier containing the separated antigen binding protein, a cell containing the nucleic acid or the carrier, a method for preparing the separated antigen binding protein, and use of the separated antigen binding protein.

The present disclosure generally relates to methods of treating cancer by administering an MCL-1 inhibitor and an antibody-drug conjugate.

The present disclosure relates to methods of using antibody conjugates with binding specificity for BCMA (BCMA) and its isoforms and homologs in combination with a gamma secretase inhibitor (GSI), such as in therapeutic methods. Also provided are pharmaceutical compositions and kits comprising the antibody conjugates and GSI.

The present invention provides cell-targeting molecules which can deliver a CD8+ T-cell epitope cargo to the MHC class I presentation pathway of the 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.

The present disclosure relates to compositions and therapeutic methods for activating an immune response in a patient in need thereof. In a preferred embodiment, the subject methods and compositions are able to antagonize the activity of VISTA, a naturally occurring “checkpoint” protein which contributes to immune tolerance, optionally in combination with an antagonist of a second checkpoint pathway such as PD-1. For example, such methods and compositions may be suitable for preventing and treating colon cancer or another cancer. An exemplary VISTA antagonist, specifically, an anti-VISTA antibody, is demonstrated herein to activate an immune response against cancer cells in vitro and in vivo, thereby conferring protective anti-tumor immunity which decreased tumor burden. Additionally, an additive benefit was observed when a VISTA antagonist was used in combination with a second checkpoint protein antagonist, specifically, an antibody against PD-1 ligand (PD-L1).

The present disclosure relates to a linker molecule for targeting molecule-drug conjugate, and the corresponding conjugate, the preparation and use thereof.