Linker-drug compounds and antibody-drug conjugates that bind to human oncology targets are disclosed. The linker-drug compounds and antibody-drug conjugates comprise a herboxidiene splicing modulator drug moiety. The disclosure further relates to methods and compositions for use in the treatment of neoplastic disorders by administering the antibody-drug conjugates provided herein. The herboxidiene itself is also claimed. Further claims are directed to its use, and to the use of a neoantigen, generated by the herboxidiene or its ADC, or a vaccine against this neoantigen.

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.

Aspects of the disclosure relate to a method for treating EGFR-mutant non-small-cell lung cancer (NSCLC) in a patient comprising administering a CD70 targeting molecule to the patient. Further aspects of the disclosure relate to a method for treating an epithelial-to-mesenchymal transition (EMT)-positive NSCLC in a patient comprising administering a CD70-targeting molecule to the patient.

The present invention relates to an antigen-binding protein, or an antigen-binding fragment thereof which binding to CEACAM6, comprising (i) a heavy chain variable domain comprising a VHCDR1 having the amino acid sequence GNTFTSYVMH; a VHCDR2 having the amino acid sequence YINPYNDGTKYNEKFKG; and a VHCDR3 having the amino acid sequence STARATPYFYAMDY and (ii) a light chain variable domain comprising a VLCDR1 having the amino acid sequence KSSQSLLWSVNQNSYLS, a VLCDR2 having the amino acid sequence GASIRES, and a VLCDR3 having the amino acid sequence QHNHGSFLPYT. The present invention also relates to compositions comprising the antigen-binding protein, or antigen-binding fragment thereof, methods of use of the antigen-binding protein, or antigen-binding fragment thereof for cancer treatment, prevention or detection and a kit comprising the antigen-binding protein, or antigen-binding fragment thereof.

The present invention concerns compositions and methods of use of bispecific antibodies comprising at least one binding site for a tumor-associated antigen (TAA) and at least one binding site for an antigen expressed on an effector T cell, NK cell, monocyte or neutrophil. The bispecific antibodies are of use for inducing an immune response against a TAA-expressing tumor. The methods may comprising administering the bispecific antibody in combination with one or more therapeutic agents such as antibody-drug conjugates, interferons (preferably interferon-α), and/or checkpoint inhibitor antibodies. The bispecific antibody is capable of targeting effector T cells, NK cells, monocytes or neutrophils to induce leukocyte-mediated cytotoxicity of cancer cells. The cytotoxic immune response is enhanced by co-administration of interferon, checkpoint inhibitor antibody and/or ADC. In preferred embodiments, the checkpoint inhibitor is a chimeric or humanized anti-PD1 antibody as described herein.

This disclosure provides NaPi2b-targeted antibody-drug conjugates (e.g., NaPi2b-targeted antibody-polymer-drug conjugates) that specifically bind to the extracellular region of SLC34A2, and to methods of using such conjugates in a variety of therapeutic, diagnostic, and prophylactic indications.

Antibodies are provided which specifically bind human and Macaca fascicularis lysosomal-associated membrane protein 1 (LAMP1) proteins and immunoconjugates comprising said antibodies conjugated or linked to a growth inhibitory agent. Pharmaceutical compositions comprising antibodies or immunoconjugates of the invention and use of the antibodies or immunoconjugates for the treatment of cancer are also provided, as well as LAMP1 antibodies, isolated nucleic acids, vectors and host cells comprising a sequence encoding said antibodies and the use of said antibody as a diagnostic tool. The application further provides for the detection of LAMP1 gene amplification or gain in cancer cells leading to the determination if patients with cancer are likely to respond to anti-LAMP1 therapy. Anti-LAMP1 therapeutic agent for use for treating cancer in a patient harboring LAMP1 gene copy number gain in cancer cells is further provided.

The present disclosure provides methods of treating cancer in a patient determined to have a HER2 mutation, such as an insertion mutation, by administering a third-generation tyrosine kinase inhibitor, such as poziotinib, in combination with a HER2 anti-body-drug conjugate.

The present disclosure relates generally to antibody-drug conjugates comprising monoclonal antibodies that specifically bind the human B7-H4 in soluble form, or membrane bound (i.e., when expressed on a cell surface) and to methods of using these conjugates as therapeutics and/or diagnostics.

The disclosure generally relates to antibodies and antibody fragments that specifically bind human EpCAM, EpCAM activatable antibodies, and immunoconjugates thereof, as well as, methods of making and using the antibodies, antibody fragments, activatable antibodies, and immunoconjugates, for the diagnosis and treatment of diseases such as cancer.