The present invention relates to humanized or chimeric antibodies binding CD3. It furthermore relates to bispecific antibodies, compositions, pharmaceutical compositions, use of said antibodies in the treatment of a disease, and method of treatment.

The present invention relates to novel human CD3 antigen-binding polypeptides and their preparation and use in the treatment and/or diagnosis of various diseases, and also relates to bispecific antibody molecules capable of activating immune effector cells and their use in diagnosis and/or treatment of various diseases.

The disclosure provides for antibodies that bind CD40, including a humanized antibody and a chimeric antibody with different Fc domains. The antibodies bind CD40 and do not exhibit CD40 agonist activity. The antibodies may comprise a modified IgG1 Fc domain, and exhibit minimal activation of immature dendritic cells. Compositions comprising antibodies, methods of use for treatment of diseases involving CD40 activity, and use in the preparation of a medicament for treatment of a disease involving CD40 activity are provided.

Described herein are, proteins comprising amino acid substitutions in at least one of a first and a second polypeptide chain. Furthermore, is described the uses and methods related to said proteins.

It was discovered that the use of an antigen-binding molecule having a cancer-specific antigen-binding domain, and a TNF superfamily-binding domain or a TNF receptor superfamily-binding domain enables agonist activity against a factor belonging to the TNF superfamily or the TNF receptor superfamily to be exhibited only in the presence of cancer-specific antigen-expressing cells, thus leading to activation of immune cells and thereby maintain anti-tumor activity while avoiding side effects such as hepatotoxicity. It was also discovered that concomitant use of the antigen-binding molecule with an antigen-binding molecule having a cancer-specific antigen-binding domain and a T cell receptor complex-binding domain can avoid side effects while increasing the anti-tumor activity.

The present invention provides Fc-fused protein constructs, which as monovalent dimers have a higher serum half-life compared to a native/natural molecule, and are, therefore, advantageous for achieving higher titers of the proteins during production, higher stability during storage, and improved efficacy when used as a therapeutic. Also provided are Fc-fused protein constructs having mutations in the Fc region that reduce effector functions, which have increased activity to inhibit tumor growth and are, therefore, advantageous when used as a cancer therapy.

The present disclosure includes a fusion protein, called a “Seldeg”, including a targeting component that specifically binds to a cell surface receptor or other cell surface molecule at near-neutral pH, and an antigen component fused directly or indirectly to the targeting component. The antigen component is configured to specifically bind a target antigen-specific antibody. The present disclosure also includes a method of depleting a target antigen-specific antibody from a patient by administering to the patient a Seldeg having an antigen component configured to specifically bind the target antigen-specific antibody.

Provided are inhibitors of diacylglycerol kinases (DGK) and methods for treating diseases that would benefit from the stimulation of the immune system, such as cancer and infections diseases, comprising administering a DGK inhibitor in combination with an antagonist of the PD 1/PD-L 1 axis and/or an antagonist of CTLA4.

Disclosed are a CD3-targeting antibody, a bispecific antibody and the use thereof. The CD3-targeting antibody comprises a light chain variable region (VL) and a heavy chain variable region (VH). The VL has the amino acid sequence as shown in SEQ ID NO: 56 or a mutation thereof. The VH has mutations on the amino acid sequence as shown in SEQ ID NO: 42, and the mutations occur at one or more of the sites of amino acid residues selected from positions 30, 73, 76, 78, 93 and 94. The bispecific antibody comprises a first protein functional region and a second protein functional region, wherein the first protein functional region comprises the CD3-targeting antibody as described above. The CD3-targeting antibody reduces the toxicity caused by cytokine release syndrome, and the bispecific antibody prepared therefrom is stable and has the ability to bind to T cells, and also reduces the difficulty of producing.

The present invention is directed to bispecific humanized PLAP (placental alkaline phosphatase)-CD3 epsilon chain (CD3e) antibodies. The present invention is further directed to a method for treating PLAP-positive cancer cells by administering the bispecific PLAP-CD3e antibody to the patients.