Combined Therapy of CTLA-4 and B7-H3

Introduction to B7-H3

B7-H3 is an immune checkpoint protein with a length of 316 AA. It consists of an extracellular domain, a transmembrane domain, as well as an intracellular domain. Previous studies have demonstrated that B7-H3 plays a significant role in inhibiting the activation of T cells and natural killer (NK) cells. The activation of B7-H3 is also associated with the cytokine release of macrophages and the poor outcomes in autoimmune diseases.

In addition, B7-H3 can be expressed in multiple types of tumors, such as melanoma and liver cancer. Moreover, recent reports have revealed that B7-H3 has been regarded as a key negative mediator for tumor development. Inhibition of the immune checkpoint molecule B7-H3 can effectively inhibit tumor growth in many cancer models. Thus, B7-H3 serves as an attractive potential target for drug development and cancer immunotherapy. For example, a variety of therapies targeting B7-H3, including antibodies and small molecule drugs, have been generated. These strategies have indicated a strong antitumor effect and relatively high safety profiles both in preclinical trials and clinical trials.

B7-H3 and CTLA-4

Over the past few years of studies, many studies have shown that immune evasion is the main cause for tumor occurrence, development, and even metastasis. Cytotoxic T-lymphocyte antigen 4 (CTLA-4), also known as CD152, is a suppressor of T-cell-mediated immune responses that have been linked to a panel of human inflammatory processes, like autoimmune diseases and cancers. Furthermore, several kinds of research have indicated that CTLA-4 can reduce T cell activation by binding the stimulatory CD80/CD86 complex of antigen-presentation cells (APCs) with a higher affinity than normal CD28. In general, B7-H3 can also be expressed on APCs to inhibit the activation of T cells. In this condition, B7-H3 and CTLA-4 may exert synergistic effects on each other, making them potential targets for combined therapy in cancer treatment.

Combined Therapy of Anti-CTLA-4 and Anti-B7-H3

Based on multiple databases, it seems that B7-H3 and CTLA-4 should be the perfect group for combination therapy development. In melanoma models, blocking B7-H3 with a specific monoclonal antibody can trigger enough anti-tumor immunity. Additionally, the combined therapy using anti-B7-H3 and anti-CTLA-4 antibodies can reduce tumor size and tumor weight. Therefore, combined therapy of anti-CTLA-4 and anti-B7-H3 antibodies shows much stronger anti-tumor effects than monotherapy alone.

Nowadays, scientists at Creative Biolabs provide a full range of novel immune checkpoint therapy development services based on diverse immune checkpoints, such as CTLA-4, B7-H3, and GITR. Our technology offers a broadly applicable combination treatment for a wide range of disease types. We are always committed to bringing deep domain expertise to assist our clients in achieving their strategic and operational objectives. Please feel free to contact us for more information.

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