The present invention relates to a conjugate of a cytotoxic drug/molecule to a cell-binding molecule with a bis-linker (a dual-linker) containing a 2,3-diaminosuccinyl group. It also relates to preparation of the conjugate of a cytotoxic drug/molecule to a cell-binding molecule with the bis-linker, particularly when the drug having functional groups of amino, hydroxyl, diamino, amino-hydroxyl, dihydroxyl, carboxyl, hydrazine, aldehyde and thiol for conjugation with the bis-linker in a specific manner, as well as the therapeutic use of the conjugates.

The invention provides an immunoconjugate comprising an antibody construct which includes an antigen binding domain and an Fc domain, an adjuvant moiety, and a linker, wherein each adjuvant moiety is covalently bonded to the antibody via the linker. Methods for treating cancer with the immunoconjugates of the invention are also described.

Provided are compositions, combinations, and methods and uses for treating a subject having a tumor, lesion or cancer. In some aspects, the methods and uses include administering a targeting molecule that binds PD-L1, conjugated with phthalocyanine dye, such as IR700. In some aspects, after administration of the conjugate, a target area is illuminated with a wavelength of light suitable for the activation of the conjugate. In some aspects, the illumination leads to the killing of PD-L1-expressing cells. The provided embodiments result in growth inhibition, volume reduction, and elimination of tumors, lesions or cancers, including metastatic tumor cells, invasive tumor cells, heterogeneous tumors and/or tumors that are not responsive to and/or resistant to other therapies. The disclosure also relates to compositions, combinations, methods and uses for enhancing immune responses, such as anti-tumor or anti-cancer immune responses, for responses against tumor growth and for effective treatment of tumors, lesions or cancers.

Methods are provided for identifying and selecting antibodies that are internalized into cells via the macropinocytosis pathway. Additionally antibodies that are internalized via this pathway are provided as well as immunoconjugates comprising such antibodies.

Antibody drug conjugates (ADC's) that bind to 191P4D12 protein and variants thereof are described herein. 191P4D12 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, the ADC's of the invention provide a therapeutic composition for the treatment of cancer.

The disclosure relates generally to polyglutamated antifolates, formulations containing liposomes filled with the polyglutamated antifolates, methods of making the polyglutamated antifolates and liposome containing formulations, and methods of using the polyglutamated antifolates and liposome containing formulations to treat hyerproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

The disclosure provides conjugates of an isolated humanized anti-CD22 antibody and PBD dimers.

Provided is an isolated CTLA4 monoclonal antibody. The antibody can highly-specifically bind to CTLA4, and can effectively block the binding of CTLA4 to B7, reduce the activity or expression level of CTLA4, relieve the inhibition of CTLA4 on the immune function of an organism, activate T lymphocytes, and effectively treat tumors and immune system diseases. Also provided are a monoclonal antibody conjugate comprising the pharmaceutical composition and diagnostic composition of the antibody, and the use thereof in the preparation of a drug for preventing and/or treating and/or treating in combination tumors and immune system diseases.

The disclosure relates generally to polyglutamated antifolates, formulations containing liposomes filled with the polyglutamated antifolates, methods of making the polyglutamated antifolates and liposome containing formulations, and methods of using the polyglutamated antifolates and liposome containing formulations to treat hyperproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

The applications provides the anti-CD3 monoclonal antibodies, antigen-binding portions thereof, therapeutic compositions thereof and/or nucleic acid encoding the same, and their use to active CD3+ T-cells to enhance cell-mediated immune responses in the treatment of cancer and other T-cell dysfunctional disorders.