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.

Provided in the present invention is a bispecific antibody which comprises an anti-MUC1 VHH antibody fragment and an anti-CD16 VHH antibody fragment. The antibody fragment used in the present invention is a variable region sequence derived from a heavy chain camelid antibody and has a high binding affinity to the antigen. Antibody fragments recognizing MUC1 and CD16 are constructed in the same antibody molecule by the invention, so that the antibody molecule can specifically bind to MUC1 and CD16 molecules to promote the killing effect of NK cells on MUC1-positive expression cells and has an inhibiting effect on the growth of MUC1-positive tumors. Also provided is a conjugate of the bispecific antibodies, a related pharmaceutical composition and use.

The present invention relates to an anti-MUC1 antibody binding specifically to Mucin 1 (MUC1) or an antigen-binding fragment thereof, an antibody-drug conjugate or bispecific antibody comprising the antibody, a pharmaceutical composition for prevention or treatment of cancer, comprising the same antibody, conjugate or bispecific antibody, and a nucleic acid encoding the same antibody, a vector and a host cell, both carrying the same nucleic acid, and a method for preparing an anti-MUC1 antibody or an antigen-binding fragment thereof, using the same vector and host cell. According to the present invention, the antibody shows outstanding affinity and binding force to MUC1 and the antibody-drug conjugate can bind specifically to a MUC1-expressing cell to specifically or selectively transfer the drug with efficacy. Therefore, the anti-MUC1 antibody and the antibody-drug conjugate according to the present invention can be usefully applied to the treatment of a MUC1-related disease, for example, cancer.

Provided herein are recombinant nucleic acids encoding T cell receptor (TCR) fusion proteins (TFPs), modified human immune cells expressing the encoded molecules, and methods of use thereof for the treatment of diseases, including cancer.

The RI-labeled anti-MUC5AC humanized antibody of the present invention is a conjugate of a chelating agent chelated with a radionuclide and an antibody (the radionuclide is a metal nuclide that emits α particle or positron, and the antibody is a humanized antibody specifically binding to MUC5AC), and is superior in specificity for MUC5AC and accumulation in tumor. Therefore, it is extremely useful for the treatment and/or diagnosis of diseases in which MUC5AC is overexpressed, particularly cancer.

The present invention relates to the fields of life sciences and medicine. Specifically, the invention relates to cancer therapies of humans. More specifically, the present invention relates to an oncolytic adenoviral vector encoding a bispecific monoclonal antibody. Furthermore, the present invention relates to methods and uses utilizing the oncolytic adenoviral vectors, also together with adoptive cell therapies.

Mucin 16 (MUC16) is highly expressed in ovarian cancer and expression on cancer cells is shown to protect tumor cells from the immune system. The present invention provides novel full-length human IgG antibodies that bind to human and MUC16 (monospecific antibodies). The present invention also provides novel bispecific antibodies (bsAbs) that bind to both MUC16 and CD3 and activate T cells via the CD3 complex in the presence of MUC16-expressing tumors. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human and monkey CD3, and a second antigen-binding molecule that specifically binds human and monkey MUC16. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing MUC16. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced MUC16-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of various cancers, including ovarian cancer. The present invention also includes anti-MUC16 antibody drug conjugates which inhibit tumor growth in vivo. In some embodiments, the anti-MUC16 antibodies are useful in diagnostic methods for identifying the presence of MUC16 in tissue and/or plasma samples.

The present invention relates to an anti-MUC1 antibody binding specifically to Mucin 1 (MUC1) or an antigen-binding fragment thereof, an antibody-drug conjugate or bispecific antibody comprising the antibody, a pharmaceutical composition for prevention or treatment of cancer, comprising the same antibody, conjugate or bispecific antibody, and a nucleic acid encoding the same antibody, a vector and a host cell, both carrying the same nucleic acid, and a method for preparing an anti-MUC1 antibody or an antigen-binding fragment thereof, using the same vector and host cell. According to the present invention, the antibody shows outstanding affinity and binding force to MUC1 and the antibody-drug conjugate can bind specifically to a MUC1-expressing cell to specifically or selectively transfer the drug with efficacy. Therefore, the anti-MUC1 antibody and the antibody-drug conjugate according to the present invention can be usefully applied to the treatment of a MUC1-related disease, for example, cancer.

The present disclosure generally relates to, among other things, a new class of receptors engineered to modulate transcriptional regulation in a ligand-dependent manner Particularly, the new receptors, even though derived from Notch and Robo, do not require the Notch or Robo regulatory regions previously believed to be necessary for the functioning of the receptors. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various health conditions such as diseases (e.g., cancers).