Abstract: The application provides anti-4-1BB monoclonal antibodies, antigen binding portions thereof, therapeutic compositions thereof and/or nucleic acid encoding the same, and their use to upregulate the function of T-cells to enhance cell-mediated immune responses in the treatment of cancer and other T-cell dysfunctional disorders.

Abstract: The application provides anti-4-1BB monoclonal antibodies, antigen binding portions thereof, therapeutic compositions thereof and/or nucleic acid encoding the same, and their use to upregulate the function of T-cells to enhance cell-mediated immune responses in the treatment of cancer and other T-cell dysfunctional disorders.

Abstract: The disclosure provides a tetra-specific antibody monomer having a N-terminal and a C-terminal, comprising in tandem from the N-terminal to the C-terminal, a first scFv domain at the N-terminal, a Fab domain, a Fc domain, a second scFv domain, and a third scFv at the C-terminal, wherein the first scFv domain, the Fab domain, the second scFv domain, and the third scFv domain each has a binding specificity against a different antigen. In one embodiment, the antigen is a tumor antigen, an immune signaling antigen, or a combination thereof. Multi-specific antibodies comprising the disclosed tetra-specific antibodies are also provided.

Abstract: The application provides tri-specific antibody monomers having a N-terminal and a C-terminal, comprising in tandem from the N-terminal to the C-terminal, a first scFv domain at the N-terminal, a Fab domain, a Fc domain, and a second scFv domain at the C-terminal. In one embodiment, the first scFv domain, the Fab domain, and the second scFv domain each has a binding specificity against a different antigen.

Abstract: The application provides tri-specific antibody monomers having a N-terminal and a C-terminal, comprising in tandem from the N-terminal to the C-terminal, a first scFv domain at the N-terminal, a Fab domain, a Fc domain, and a second scFv domain at the C-terminal. In one embodiment, the first scFv domain, the Fab domain, and the second scFv domain each has a binding specificity against a different antigen.

Abstract: 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.

Abstract: The application provides multi-specific antibody-like proteins may comprising one or more binding domains including a first binding domain (D1), a second binding domain (D2), a third binding domain (D3), a fourth binding domain (D4), a fifth binding domain (D5), or a sixth binding domain (D6). The multi-specific antibody-like protein disclosed herein may be mono-specific, bi-specific, tri-specific, tetra-specific, penta-specific or hexa-specific. The binding domains such as D1, D2, D3, D4, D5, and D6 may each independently have a binding affinity to specificity against a T cell activating receptor, an immune cell receptor, an immune checkpoint molecule, a co-stimulation factor, a receptor of a leukocyte, a tumor antigen, a tumor associated antigen (TAA), a receptor of a tissue cell, a receptor of a cancer cell, or a combination thereof.

Abstract: The application provides the anti-PD-L1 monoclonal antibodies, antigen binding portions thereof, therapeutic compositions thereof and/or nucleic acid encoding the same, and their use to upregulate the function of T-cells to enhance cell-mediated immune responses in the treatment of cancer and other T-cell dysfunctional disorders.

Abstract: The application provides a multi-specific antibody-like protein having a N-terminal and a C-terminal, comprising in tandem from the N-terminal to the C-terminal, a first binding domain (D1) at the N-terminal, a second binding domain (D2) comprising a light chain moiety, a Fc region, a third binding domain (D3), and a fourth binding domain (D4) at the C-terminal, wherein the light chain moiety comprises a fifth binding domain (D5) covalently attached to the C-terminal, a sixth binding domain (D6) covalently attached to the N-terminal, or both, and wherein the D1, D2, D3, D4, D5 and D6 each has a binding specificity against a tumor antigen, an immune signaling antigen, or a combination thereof.

Abstract: 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.

Abstract: The application provides anti-ROR1 monoclonal antibodies, antigen binding portions thereof, therapeutic compositions thereof and/or nucleic acid encoding the same, and their use to upregulate the function of T-cells to enhance cell-mediated immune responses in the treatment of cancer and other T-cell dysfunctional disorders.

Abstract: The application provides anti-PD-1 monoclonal antibodies, antigen binding portions thereof, therapeutic compositions thereof and/or nucleic acid encoding the same, and their use to upregulate the function of T-cells to enhance cell-mediated immune responses in the treatment of cancer and other T-cell dysfunctional disorders.

Abstract: The application provides the anti-PD-L1 monoclonal antibodies, antigen binding portions thereof, therapeutic compositions thereof and/or nucleic acid encoding the same, and their use to upregulate the function of T-cells to enhance cell-mediated immune responses in the treatment of cancer and other T-cell dysfunctional disorders.

Abstract: The disclosure provides a tetra-specific antibody monomer having a N-terminal and a C-terminal, comprising in tandem from the N-terminal to the C-terminal, a first scFv domain at the N-terminal, a Fab domain, a Fc domain, a second scFv domain, and a third scFv at the C-terminal, wherein the first scFv domain, the Fab domain, the second scFv domain, and the third scFv domain each has a binding specificity against a different antigen. In one embodiment, the antigen is a tumor antigen, an immune signaling antigen, or a combination thereof. Multi-specific antibodies comprising the disclosed tetra-specific antibodies are also provided.

Abstract: The application provides guidance and navigation control (GNC) proteins. In one embodiment, the GNC protein Comprises a T-cell binding moiety and a cancer-targeting moiety, wherein the T-cell binding moiety has a binding specificity to a T-cell receptor comprising CD3, CD28, PDL1, PD1, OX40, 4-1BB, GITR, TIGIT, TIM-3, LAG-3, CTLA4, CD40, VISTA, ICOS, BTLA, Light, NKp30, CD28H, CD27, CD226, CD96, CD112R, A2AR, CD160, CD244, CECAM1, CD200R, TNFRSF25 (DR3), or a combination thereof, and wherein the cancer targeting moiety has a binding specificity to a cancer cell receptor.

Abstract: The application provides anti-ROR1 monoclonal antibodies, antigen binding portions thereof, therapeutic compositions thereof and/or nucleic acid encoding the same, and their use to upregulate the function of T-cells to enhance cell-mediated immune responses in the treatment of cancer and other T-cell dysfunctional disorders.

Abstract: The application provides anti-4-1BB monoclonal antibodies, antigen binding portions thereof, therapeutic compositions thereof and/or nucleic acid encoding the same, and their use to upregulate the function of T-cells to enhance cell-mediated immune responses in the treatment of cancer and other T-cell dysfunctional disorders.

Abstract: The application provides guidance and navigation control (GNC) proteins. In one embodiment, the guidance and navigation control (GNC) protein, comprising a binding domain for a T cell activating receptor, a binding domain for a tumor associated antigen, a bind domain for an immune checkpoint receptor, and a binding domain for a T cell co-stimulating receptor. The binding domain for the tumor associated antigen is not adjacent to the binding domain for the T cell co-stimulating receptor. In one embodiment, the binding domain for the T cell activating receptor is adjacent to the binding domain for the tumor associated antigen (TAA).

Abstract: The disclosure provides bispecific antibodies having the binding specificity to at least two of human CTLA4, PD-1 or PD-L1. In one embodiment, the bispecific antibody comprises IgG domains having heavy chains and light chains, and two scFv components being connected to either C-terminal of the heavy chains or N-terminal of the light chains, wherein the IgG domains have the binding specificity to a first antigen, wherein the scFv components have the binding specificity to a second antigen, and wherein the first antigen and the second antigen are different and are independently selected from a-CTLA4, ?-PD-1, and ?-PD-L1.

Abstract: The application provides anti-PD-1 monoclonal antibodies, antigen binding portions thereof, therapeutic compositions thereof and/or nucleic acid encoding the same, and their use to upregulate the function of T-cells to enhance cell-mediated immune responses in the treatment of cancer and other T-cell dysfunctional disorders.