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: 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 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 present invention provides a newly identified B7 receptor, zB7R1 that functions as lymphocyte inhibitory receptor, which is a PD-1-like molecule and is expressed on T cells. The present invention also provides the discovery of zB7R1's ability to bind to CD155. Methods and compositions for modulating zB7R1-mediated negative signaling and interfering with the interaction of its counter-receptor for therapeutic, diagnostic and research purposes are also provided.

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 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 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 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: A bispecific tetravalent antibody comprising an IgG having a pair of heavy chains and a pair of light chains, and two scFv components being connected to either C or N terminals of the heavy or light chains. The bispecific tetravalent antibody may have a binding specificity for two different members of EGFR family.

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: A bispecific tetravalent antibody comprising an IgG having a pair of heavy chains and a pair of light chains, and two scFv components being connected to either C or N terminals of the heavy or light chains. The bispecific tetravalent antibody may have a binding specificity for two different members of EGFR family.

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 application provides methods for generating a therapeutic composition. The method includes the steps of providing a cell material comprising a cytotoxic cell, incubating the cell material with a first GNC protein to provide an activated cell composition, wherein the activated cell composition comprises a first therapeutic cell, and formulating the activated cell composition to provide a therapeutic composition, wherein the therapeutic composition is substantially free of exogenous viral and non-viral DNA or RNA. The first GNC protein comprises a first cytotoxic binding moiety and a first cancer targeting moiety, wherein the first cytotoxic binding moiety has a specificity to a first cytotoxic cell receptor and is configured to activate the first cytotoxic cell, and wherein the first cancer targeting moiety has a specificity to a first cancer cell receptor. The first therapeutic cell comprises the first GNC protein bound to the cytotoxic cell through the first cytotoxic cell receptor.

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.