The present invention provides EpCAM antibodies with different affinities. The present invention also provides chimeric antigen receptors (CARs) specific to EpCAM. CAR T cells comprising human EpCAM scFv having a low and sufficient affinity to EpCAM can avoid targeting healthy tissues with low EpCAM expression while exhibiting long-term efficacy against tumor tissues with high EpCAM expression. The present invention also relates to an adoptive cell therapy method for treating cancer by administering the CAR-T cells comprising human EpCAM scFv to a subject suffering from cancer, whereby the CAR T cells bind to the cancer cells overexpressing EpCAM and kill the cancer cells.

The present invention provides EpCAM antibodies with different affinities. The present invention also provides chimeric antigen receptors (CARs) specific to EpCAM. CAR T cells comprising human EpCAM scFv having a low and sufficient affinity to EpCAM can avoid targeting healthy tissues with low EpCAM expression while exhibiting long-term efficacy against tumor tissues with high EpCAM expression. The present invention also relates to an adoptive cell therapy method for treating cancer by administering the CAR-T cells comprising human EpCAM scFv to a subject suffering from cancer, whereby the CAR T cells bind to the cancer cells overexpressing EpCAM and kill the cancer cells.

Antigen binding molecules (ABMs) comprising Fab domains in non-native configurations, ABM conjugates comprising the ABMs and cytotoxic or cytostatic agents, pharmaceutical compositions containing the ABMs and ABM conjugates, methods of using the ABMs, ABM conjugates and pharmaceutical compositions for treating cancer, nucleic acids encoding the ABMs, cells engineered to express the ABMs, and methods of producing ABMs.

The present invention relates to novel humanized anti-IL-4 and IL-13 antibodies and fragments thereof and novel bispecific antibodies and fragments thereof that specifically bind to IL-4 and IL-13. The invention also includes uses of the antibodies to treat or prevent IL-4 and/or IL-13 mediated diseases or disorders, including allergic asthma and dermatitis.

The present invention relates to a method for the treatment, amelioration or elimination of pediatric acute lymphoblastic leukemia (ALL), the method comprising the administration of a pharmaceutical composition comprising a CD19×CD3 bispecific single chain antibody construct to a pediatric ALL patient in the need thereof.

Herein is reported a method for determining the binding of an antibody, which comprises a first binding site specifically binding to a first antigen and a second binding site specifically binding to a second antigen, to said first and said second antigen, wherein the method comprises the steps of capturing the antibody on a solid phase using a capture reagent specifically binding to a constant domain of the antibody, incubating the captured antibody with the first or the second antigen to form a captured antibody-antigen complex and determining a first binding signal, either i) incubating the captured antibody-antigen complex with the antigen not used for the formation of the captured antibody-antigen complex to form a captured antibody-antigen-antigen complex and determining a second binding signal, or ii) regenerating the surface, capturing the antibody on a solid phase using a capture reagent specifically binding to a constant domain of the antibody, incubating the captured antibody with the antigen not used for the formation of the captured antibody-antigen complex in step b) to form a captured antibody-antigen-antigen complex and determining a third binding signal, and determining the overall or individual binding of the antibody to the first and the second antigen from the first binding signal and the second or third binding signal.

The disclosure provides engineered polypeptides that specifically bind to human complement component C5 and/or serum albumin. The disclosure also provides fusion proteins comprising such engineered polypeptides, wherein such fusion proteins may be multivalent and multi-specific fusion proteins. The disclosure further provides nucleic acid molecules that encode such engineered polypeptides or fusion proteins, and methods of making such engineered polypeptides or fusion proteins. The disclosure further provides pharmaceutical compositions that comprise such engineered polypeptides or fusion proteins, and methods of treatment using such engineered polypeptides or fusion proteins.

The present invention provides novel antibodies and antigen binding fragments thereof that bind to human CD30. Also presented are single chain variable antibodies, chimeric antigen receptors and uses thereof. Methods of treating cancer are also disclosed.

Provided are a bispecific antibody and use thereof. The bispecific antibody comprises a B7-H4-targeting antigen-binding domain and a 4-1BB-targeting antigen-binding domain. The bispecific antibody has one or two or three sites for binding to 4-1BB, along with a novel fully human B7-H4 antibody. The bispecific antibody specifically binds to tumor cells by targeting B7-H4, reducing toxicity induced by 4-1BB activation. In addition, the bispecific antibody of the present invention comprises a human Fc fragment, and thus retains the binding of Fc to FcRn and has a longer half-life.

The present invention provides methods for treating, reducing the severity, or inhibiting the growth of cancer (e.g., ovarian cancer or pancreatic cancer). The methods of the present invention comprise administering to a subject in need thereof a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to immunomodulatory receptor cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) in combination with a therapeutically effective amount of a bispecific antibody that specifically binds Mucin 16 (MUC16) and CD3.