Provided is a high-affinity T cell receptor (TCR) that recognizes SSX2, wherein the TCR has the property of binding to a KASEKIFYV (SEQ ID NO: 29)-HLA A0201 complex, and the binding affinity of the TCR to the KASEKIFYV (SEQ ID NO: 29)-HLA A0201 complex is at least twice the binding affinity of a wild-type TCR to the KASEKIFYV (SEQ ID NO: 29)-HLA A0201 complex. Also provided is a fusion molecule of such a TCR with a therapeutic agent. Such a TCR can be used alone or in combination with a therapeutic agent to target tumor cells presenting the KASEKIFYV (SEQ ID NO: 29)-HLA A0201 complex.

Disclosed is a humanized 4-1BB monoclonal antibody, an antigen-binding fragment thereof, a pharmaceutical composition and a medical use thereof. The monoclonal antibody comprises CDR1 with the amino acid sequence shown in SEQ ID NO: 1 or SEQ ID NO: 4, CDR2 with the amino acid sequence shown in SEQ ID NO: 2 or SEQ ID NO: 5, CDR3 with the amino acid sequence shown in SEQ ID NO: 3, CDR1′ with the amino acid sequence shown in SEQ ID NO: 6, CDR2′ with the amino acid sequence shown in SEQ ID NO: 7, CDR3′ with the amino acid sequence shown in SEQ ID NO: 8. The monoclonal antibody binds to human 4-1BB with high affinity and specificity, leads to a significant increase in T cell proliferation and TNF-γ production, and enhances and stimulates human 4-1BB-mediated immune response.

A multispecific antibody is provided. The antibody comprising a first moiety, which binds and activates CD40, a second moiety, which specifically binds a dendritic cell (DC) and a third moiety comprising a modified Fc region of the multispecific antibody for enhancing specificity and affinity of binding to FcγRIIb and uses of same.

Provided are anti-CD137 constructs that bind to CD137, including multispecific anti-CD137 antibodies with binding specificity for CD137 and one or more additional antigens, and methods of using the same. In certain embodiments, the one or more additional antigens comprise human epidermal growth factor receptor 2 (HER2).

The present disclosure relates to compositions and therapeutic methods for activating an immune response in a patient in need thereof. In a preferred embodiment, the subject methods and compositions are able to antagonize the activity of VISTA, a naturally occurring “checkpoint” protein which contributes to immune tolerance, optionally in combination with an antagonist of a second checkpoint pathway such as PD-1. For example, such methods and compositions may be suitable for preventing and treating colon cancer or another cancer. An exemplary VISTA antagonist, specifically, an anti-VISTA antibody, is demonstrated herein to activate an immune response against cancer cells in vitro and in vivo, thereby conferring protective anti-tumor immunity which decreased tumor burden. Additionally, an additive benefit was observed when a VISTA antagonist was used in combination with a second checkpoint protein antagonist, specifically, an antibody against PD-1 ligand (PD-L1).

The present disclosure provides humanized antibodies, including antibodies comprising an ultralong CDR3 and uses thereof.

The present invention is directed to the field of immunotherapy. Specifically, the invention provides compositions and methods for improved T cell modulation ex vivo and in vivo and for the treatment of cancer and other pathologies. More specifically, embodiments of the invention are directed to the use of soluble NTB-A polypeptides or agonists thereof for the treatment of cancer patients, for preventing and treating cytopenia in susceptible patients, and for the ex vivo preparation of improved cell compositions.

The present invention provides isolated monoclonal antibodies (e.g., humanized and human monoclonal antibodies) that bind to human Inducible T Cell COStimulator (ICOS) and exhibit therapeutically desirable functional properties, e.g., the ability to stimulate human ICOS activity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells, and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules, and pharmaceutical compositions comprising the antibodies of the invention are also provided. The antibodies of the invention can be used, for example, as an agonist to stimulate or enhance an immune response in a subject, e.g., antigen-specific T cell responses against a tumor or viral antigen. The antibodies of the invention can also be used in combination with other antibodies (e.g., PD-1, PD-L1, and/or CTLA-4 antibodies) to treat, for example, cancer. Accordingly, the antibodies can be used in therapeutic applications and methods to detect ICOS protein.

Therapeutic use and dosing regimen of anti-ICOS antibodies or antigen-binding fragments thereof for modulating the ratio between regulatory T cells and effector T cells, stimulating the immune system of patients, and/or treating tumours or cancers, as monotherapy or combination therapy, e.g., with anti-PD-L1 antibodies or antigen-binding fragments thereof.

Provided are an anti-CD40 antibody, an antigen binding fragment thereof, and a medical use thereof. Also provided are a chimeric antibody and a humanized antibody including a CDR region of the anti-CD40 antibody, a pharmaceutical composition including the human anti-CD40 antibody and the antigen binding fragment thereof, and an application thereof as an anti-cancer drug. In particular, provided are a humanized anti-CD40 antibody, and an application thereof in preparation of a drug to treat a CD40-mediated disease or disorder.