The present invention relates to tumor targeted bispecific agonistic antigen binding molecules characterized by monovalent binding to CD28, methods for their production, pharmaceutical compositions containing these antibodies, and methods of using the same.

The present invention relates to a method for activating a cell and a cell activated thereby and a use thereof, more particularly, to an in vitro method of enhancing, recovering of immune response of CD8 T cells in exhaustion and proliferating the CD8 T cells comprising the step of inducing overexpression of Klf4 protein in CD8 T cells, a cell population containing the CD8 T cells or transduced CAR-CD8 T cells whose anticancer activity is enhanced by overexpressing Klf4 protein and use thereof.

Mesenchymal stem cells (MSCs) for use in the treatment of a tumor, wherein said treatment comprises the combined administration of said mesenchymal stem cells with an anti-tumor immunotherapy, and wherein said MSCs do not comprise exogenous nucleic acids that encode immune response-stimulating cytokines. In a preferred embodiment the invention relates to the use of said MSCs in the treatment of a tumor and/or malignant disease, wherein the anti-tumor immunotherapy for combined administration comprises the administration of a cellular immunotherapy, preferably chimeric antigen receptor (CAR) T cells, wherein said T cell receptor binds specifically to a tumor-associated antigen, and the mesenchymal stem cells are not genetically modified.

Provided are methods for clinical treatment of malignant tumors (e.g., advanced solid tumors) using a combination of an anti-LAG-3 antibody, an anti-PD-1 antibody, and an immunotherapeutic agent.

A multi-specific antibody-like protein having a first monomer comprising a first binding monomer, a CH1 domain, a first hinge, a first CH2 domain, and a first CH3 domain, a second monomer comprising a second binding monomer, a CL domain, a second hinge, a second CH2 domain, and a second CH3 domain, wherein the first binding monomer and a second binding monomer are configured to form a dimer, wherein the first monomer and the second monomer are covalently paired through at least one disulfide bond between the CH1 domain and the CL domain and at least one disulfide bond between the first hinge and the second hinge, wherein the first monomer and second monomer may comprise optionally a first binding domain (D1) and a second binding domain (D2), and a fourth binding domain (D4) and a fifth binding domain (D5), and wherein the multi-specific antibody-like protein is at least bi-specific.

The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease.

A tetravalent, homodimer-type bispecific antibody molecule that simultaneously targets immune effector cell antigen CD3 and human epidermal growth factor receptor 2 (Her2); the bispecific antibody molecule comprises, from in sequence from N-terminus to C-terminus, a first single-chain Fv capable of specifically binding to Her2, a second single-chain Fv capable of specifically binding to CD3, and an Fc fragment; the first and second single-chain Fv are connected by means of a connection peptide, and the second single-chain Fv is connected to the Fc directly fragment or is connected by means of a connection peptide; the Fc fragment does not have effector functions such as CDC, ADCC and ADCP. The bispecific antibody may significantly inhibit or kill tumor cells, and has controlled toxic side effects that may be caused by excessive activation of effector cells. The maximum safe starting dose in preclinical toxicology evaluation tests is significantly higher than other doses having the same target, and no systemic immunotoxicity occurs, suggesting that the drug administration safety window for the bispecific antibody is wide; in addition, said bispecific antibody is a homodimer that does not experience the problem of heavy chain and light chain mismatching; the steps of purification are simple and efficient, expression is high, and the physicochemical and in vivo stability of the antibody are significantly improved.

The present invention provides novel CD3 antigen binding fragments with particularly advantageous properties such as producibility, stability, binding affinity, biological activity, specific targeting of certain T cells, targeting efficiency, remaining tumor cell killing and reduced toxicity. The present invention also provides bispecific antigen binding molecules for activating T cells. In addition, the invention further provides methods of treating cancer in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising the above said bispecific antigen binding molecules.

The invention provides immunoconjugates of Formula (I) comprising an antibody linked by conjugation to one or more aminoquinoline derivatives. The invention also provides aminoquinoline derivative intermediate compositions of Formula (III) comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the immunoconjugates through a linker or linking moiety. The invention further provides methods of treating cancer with the immunoconjugates.

Provided herein are protein complexes comprising a sensor domain and a therapeutic domain linked by a linker, and methods of use thereof. In aspects of the present disclosure, activity of the therapeutic domain comprises a dependence on sensor domain binding to target markers.