The present invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a therapeutic moiety, and further relates to processes for making and using the conjugates.

The present invention concerns antibody-conjugates comprising an anti-CEACAM5-antibody for use for treating cancer in combination with folinic acid, 5-fluoro-uracil and oxaliplatin (FOLFOX). The invention further relates to pharmaceutical compositions and kit-of-parts comprising an anti-CEACAM5-antibody in combination with folinic acid, 5-fluoro-uracil and oxaliplatin (FOLFOX) for use for treating cancer.

The present invention concerns antibody-conjugates comprising an anti-CEACAM5-antibody for use for treating cancer in combination with cetuximab. The invention further relates to pharmaceutical compositions and kit-of-parts comprising an anti-CEA-CAM5-antibody in combination with cetuximab for use for treating cancer.

Aspects of the invention provide methods for harnessing the potential of proteins that occur naturally (e.g., in humans) and that have serious but finite toxicity. Aspects of the invention relate to a quantitative systems-biological and structural approach to design a class Mof chimeric proteins that avoid the toxicity of protein drugs while retaining their desired activities. In particular, chimeric proteins containing a variant form of a natural protein fused to a targeting moiety may be administered to a subject to target a signal (e.g., induction of apoptosis) to particular cells without having a generalized toxic effect.

The present invention discloses antibodies which bind human and Macaca fascicularis CEACAM5 proteins, as well as isolated nucleic acids, vectors and host cells comprising a sequence encoding said antibodies. The invention also disclosers immunoconjugates comprising said antibodies conjugated or linked to a growth-inhibitory agent, and to pharmaceutical compositions comprising antibodies, or immunoconjugates of the invention. The antibodies or immunoconjugates of the invention are used for the treatment of cancer or for diagnostic purposes.

The present invention relates to combination therapy with ADCs against a tumor-associated antigen, such as Trop-2, and drugs, such as microtubule inhibitors and/or PARP inhibitors. Where ADCs are used, they preferably incorporate SN-38 or another drug that induces DNA strand breaks. Preferably, the combination of ADC and PARPi or microtubule inhibitor exhibits synergistic effects against the cancer. The combination therapy 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.

Provided are conjugates. In certain aspects, provided are drug conjugates that include a knottin peptide comprising an engineered loop that binds to a cell surface molecule, and an anti-microtubule agent conjugated to the knottin peptide via a linker. In some aspects, provided are drug conjugates that include a fusion protein that includes a knottin peptide comprising an engineered loop that binds to a cell surface molecule, fused to an antibody subunit or fragment thereof. Such drug conjugates further include a drug conjugated to the fusion protein. Also provided are compositions and kits that include the conjugates of the present disclosure. Methods of using the conjugates, e.g., for therapeutic purposes, are also provided.

The present invention generally relates to antigen-specific immunoconjugates for selectively delivering effector moieties that influence cellular activity. More specifically, the invention provides novel immunoconjugates comprising a first antigen binding moiety, an Fc domain and a single effector moiety. In addition, the present invention relates to polynucleotides encoding such immunoconjugates, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the immunoconjugates of the invention, and to methods of using these immunoconjugates in the treatment of disease.

Provided herein, inter alia, are methods of using bispecific antibody compounds which may bind immune cells and are, inter alia, useful for treating cancers. Anti-tumor antigen antibodies are connected to anti-immune antibodies through their hinge regions using, for example, click chemistry to form dual-specific, bivalent BiTES with high in vivo tumor targeting ability and tumor cytotoxicity.

Provided is a conjugate comprising a ligand, a spacer, and a peptide linker useful for an in-vivo diagnostic drug and internal radiation therapy, using an anti-human MUC1 antibody Fab fragment whose binding activity is not attenuated even by labeling with a metal, a fluorescent dye, or the like. A conjugate comprising 3arm DOTA, a specific spacer, a specific peptide linker, and a biomolecule including an anti-human MUC1 antibody Fab fragment, wherein the binding activity thereof is not attenuated even by labeling with a metal, a fluorescent dye, or the like, can be used as a diagnostic composition and/or a pharmaceutical composition.